129 results on '"miR-25-3p"'
Search Results
2. MiR-25-3p regulates pulmonary arteriovenous malformation after Glenn procedure in patients with univentricular heart via the PHLPP2-HIF-1α axis.
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Kawamura, Junpei, Yamakuchi, Munekazu, Ueno, Kentaro, Hashiguchi, Teruto, and Okamoto, Yasuhiro
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MEDICAL sciences , *SMALL interfering RNA , *PULMONARY artery , *ARTERIOVENOUS malformation , *CHILD patients , *LUNGS - Abstract
The detailed mechanism of pulmonary arteriovenous malformations after Glenn surgery (G-PAVMs) in cyanotic congenital heart disease (CHD) remains unclear. Microarray in situ hybridization was performed to assess the miRNA (miRNA) profiles of serum from pediatric patients (0–6 years of age) with G-PAVMs and after the Fontan procedure without G-PAVMs. In addition, we investigated the tube formation, migration, and proliferation of human lung microvascular endothelial cells (HMVEC-L) transfected with miR-25-3p mimic, miR-25-3p inhibitor, or PHLPP2 small interfering RNA, and examined HIF-1α/VEGF-A signaling after hypoxic stimulation. Serum miRNAs that showed ≥ 2-fold higher levels in patients with G-PAVMs than in other patients were selected. MiR-25-3p was significantly upregulated in the pulmonary artery sera of the post-Glenn group than in the post-Fontan group. We identified PHLPP2 as a direct target of miR-25-3p. PHLPP2 expression was significantly decreased in HMVEC-L transfected with miR-25-3p mimic compared to the control cells. HIF-1α and VEGF-A expression levels were increased in HMVEC-L transfected with miR-25-3p mimic compared to the control cells in a PHLPP2/Akt/mTOR signaling-dependent manner after hypoxic stimulation. MiR-25-3p promoted HMVEC-L angiogenesis, proliferation, and migration under hypoxic conditions. MiR-25-3p in the pulmonary arteries may contribute to G-PAVM development. [ABSTRACT FROM AUTHOR] more...
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- 2025
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3. Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy.
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Lei, Li-Min, Li, Fu-Xing-Zi, Lin, Xiao, Xu, Feng, Shan, Su-Kang, Guo, Bei, Zheng, Ming-Hui, Tang, Ke-Xin, Wang, Yi, Xu, Qiu-Shuang, Ouyang, Wen-Lu, Duan, Jia-Yue, Wu, Yun-Yun, Cao, Ye-Chi, Zhou, Zhi-Ang, He, Si-Yang, Wu, Yan-Lin, Chen, Xi, Lin, Zheng-Jun, and Pan, Yi more...
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COLD (Temperature) , *LOW temperature plasmas , *EXOSOMES , *HOMEOSTASIS , *BONE growth - Abstract
Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass. [ABSTRACT FROM AUTHOR] more...
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- 2024
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4. The phosphokinase activity of IRE1ɑ prevents the oxidative stress injury through miR‐25/Nox4 pathway after ICH.
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Liao, Yuhui, Huang, Juan, Wang, Zhenhua, Yang, Zhengyu, Shu, Yue, Gan, Shengwei, Wang, Zhixu, and Lu, Weitian
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OXIDATIVE stress , *WESTERN immunoblotting , *CEREBRAL edema , *PHYSIOLOGICAL stress , *CEREBRAL hemorrhage - Abstract
Background: Endoplasmic reticulum (ER) stress and oxidative stress are the major pathologies encountered after intracerebral hemorrhage (ICH). Inositol‐requiring enzyme‐1 alpha (IRE1α) is the most evolutionarily conserved ER stress sensor, which plays a role in monitoring and responding to the accumulation of unfolded/misfolded proteins in the ER lumen. Recent studies have shown that ER stress is profoundly related to oxidative stress in physiological or pathological conditions. The purpose of this study was to investigate the role of IRE1α in oxidative stress and the potential mechanism. Methods: A mouse model of ICH was established by autologous blood injection. The IRE1α phosphokinase inhibitor KIRA6 was administrated intranasally at 1 h after ICH, antagomiR‐25 and agomiR‐25 were injected intraventricularly at 24 h before ICH. Western blot analysis, RT‐qPCR, immunofluorescence staining, hematoma volume, neurobehavioral tests, dihydroethidium (DHE) staining, H2O2 content, brain water content, body weight, Hematoxylin and Eosin (HE) staining, Nissl staining, Morris Water Maze (MWM) and Elevated Plus Maze (EPM) were performed. Results: Endogenous phosphorylated IRE1α (p‐IRE1α), miR‐25‐3p, and Nox4 were increased in the ICH model. Administration of KIRA6 downregulated miR‐25‐3p expression, upregulated Nox4 expression, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, reduced body weight, aggravated spatial learning and memory deficits, and increased anxiety levels. Then antagomiR‐25 further upregulated the expression of Nox4, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, whereas agomiR‐25 reversed the effects promoted by KIRA6. Conclusion: The IRE1α phosphokinase activity is involved in the oxidative stress response through miR‐25/Nox4 pathway in the mouse ICH brain. [ABSTRACT FROM AUTHOR] more...
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- 2024
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5. Early miR-320b and miR-25-3p miRNA levels correlate with multiple sclerosis severity at 10 years: a cohort study
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Alicia Gonzalez-Martinez, Gauruv Bose, Hrishikesh Lokhande, Shrishti Saxena, Brian C. Healy, Mariann Polgar-Turcsanyi, Howard L. Weiner, and Tanuja Chitnis
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miRNA ,Long-term ,Disability ,EDSS ,miR-320b ,miR-25-3p ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder which may cause long-term disability. MicroRNA (miRNA) are stable, non-coding molecules that have been identified in our Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB)-cohort, as well as other international cohorts, as potential disease biomarkers in MS. However, few studies have evaluated the association of miRNA expression early in the MS disease course with long-term outcomes. Therefore, we aimed to evaluate the potential role of three candidate serum miRNAs previously correlated with MS disability in patients with MS, miR-320b, miR-25-3p and miRNA 486-5p, as early biomarkers of MS disability at 10-year follow-up. Main body We included 144 patients with serum obtained within three years of MS onset. miRNA expression was measured by RNA extraction followed by RT-PCR. Demographic, clinical, brain MRI and other biomarkers were collected. The primary outcome was the association between early miRNA expression and retaining benign MS, defined as EDSS ≤ 2 at 10-year follow-up. Among the 144 patients, 104 were benign and 40 were not benign at 10-year follow-up. 89 (62%) were women, with mean age at onset 37.7 (SD: 9.6) years. Patients who retained benign MS had lower values of miR-25-3p (p = 0.047) and higher miR-320b (p = 0.025) values. Development of SPMS was associated with higher miR-320b (p = 0.002) levels. Brain parenchymal fraction at year 10 was negatively correlated with miR-25-3p (p = 0.0004) and positively correlated with miR-320b (p = 0.006). No association was found between miR-486-5p and any outcome, and 10-year T2-lesion volume was not associated with any miRNA. Conclusions Our results show that miR-320b and miR-25-3p expression are early biomarkers associated with MS severity and brain atrophy. This study provides class III evidence of that miR-320b and miR-25-3p are associated with long-term MS disability which may be a potential tool to risk-stratify patients with MS for early treatment decisions. more...
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- 2023
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6. Non-invasive diagnostic potential of salivary miR-25-3p for periodontal disease and osteoporosis among a cohort of elderly patients with type 2 diabetes mellitus
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Jing Ni, Qiong Zhang, and Fei Lei
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Type 2 diabetes mellitus ,Osteoporosis ,Periodontal disease ,miR-25-3p ,Saliva ,Dentistry ,RK1-715 - Abstract
Abstract Objective Osteoporosis (OP) and periodontal disease (PD) are two common health issues that threaten the older population and potentially connected each other in the context of type 2 diabetes mellitus (T2DM). Dysregulated expression of microRNAs (miRNAs) may contribute to the development and progression of both OP and PD among elderly T2DM patients. The present study aimed to evaluate the accuracy of miR-25-3p expression for the detection of OP and PD when compared to a mixed group of patients with T2DM. Methods The study recruited 45 T2DM patients with normal bone mineral density (BMD) and healthy periodontium, 40 type 2 diabetic osteoporosis patients coexistent with PD, 50 type 2 diabetic osteoporosis patients with healthy periodontium, and 52 periodontally healthy individuals. miRNA expression measurements in the saliva were determined by real-time PCR. Results The salivary expression of miR-25-3p was higher in type 2 diabetic osteoporosis patients than patients with T2DM only and healthy individuals (P more...
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- 2023
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7. Dysregulation of miR-25-3p in Diabetic Nephropathy and Its Role in Inflammatory Response
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Chen, Huanzhen, Tian, Tongguan, and Wang, Dan
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- 2024
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8. Early miR-320b and miR-25-3p miRNA levels correlate with multiple sclerosis severity at 10 years: a cohort study.
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Gonzalez-Martinez, Alicia, Bose, Gauruv, Lokhande, Hrishikesh, Saxena, Shrishti, Healy, Brian C., Polgar-Turcsanyi, Mariann, Weiner, Howard L., and Chitnis, Tanuja
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GENE expression ,MULTIPLE sclerosis ,MICRORNA ,DEMYELINATION ,WOMEN'S hospitals ,MYELIN sheath diseases - Abstract
Background: Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder which may cause long-term disability. MicroRNA (miRNA) are stable, non-coding molecules that have been identified in our Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB)-cohort, as well as other international cohorts, as potential disease biomarkers in MS. However, few studies have evaluated the association of miRNA expression early in the MS disease course with long-term outcomes. Therefore, we aimed to evaluate the potential role of three candidate serum miRNAs previously correlated with MS disability in patients with MS, miR-320b, miR-25-3p and miRNA 486-5p, as early biomarkers of MS disability at 10-year follow-up. Main body: We included 144 patients with serum obtained within three years of MS onset. miRNA expression was measured by RNA extraction followed by RT-PCR. Demographic, clinical, brain MRI and other biomarkers were collected. The primary outcome was the association between early miRNA expression and retaining benign MS, defined as EDSS ≤ 2 at 10-year follow-up. Among the 144 patients, 104 were benign and 40 were not benign at 10-year follow-up. 89 (62%) were women, with mean age at onset 37.7 (SD: 9.6) years. Patients who retained benign MS had lower values of miR-25-3p (p = 0.047) and higher miR-320b (p = 0.025) values. Development of SPMS was associated with higher miR-320b (p = 0.002) levels. Brain parenchymal fraction at year 10 was negatively correlated with miR-25-3p (p = 0.0004) and positively correlated with miR-320b (p = 0.006). No association was found between miR-486-5p and any outcome, and 10-year T2-lesion volume was not associated with any miRNA. Conclusions: Our results show that miR-320b and miR-25-3p expression are early biomarkers associated with MS severity and brain atrophy. This study provides class III evidence of that miR-320b and miR-25-3p are associated with long-term MS disability which may be a potential tool to risk-stratify patients with MS for early treatment decisions. [ABSTRACT FROM AUTHOR] more...
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- 2023
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9. A functional polymorphism at the miR-25-3p binding site in the 3′-untranslated region of the S1PR1 gene decreases the risk of osteoporosis in Chinese postmenopausal women
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Haoyu Yang, Chenwei Xiong, Zhentang Yu, Zhicheng Yang, Yi Zhang, Junjie Zhang, Yong Huang, Nanwei Xu, Xindie Zhou, Mengqing Jiang, and Zhonghua Xu
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MiR-25-3p ,S1PR1 ,Osteoporosis ,Osteoclast ,rs41274221 ,Polymorphism ,Chemistry ,QD1-999 - Abstract
The low bone mineral density due to abnormally activated osteoclasts can induce bone disorders such as osteopenia and osteoporosis. MiR-25-3p modulates sphingosine-1-phosphate receptor 1 (S1PR1) expression to enhance osteoclast motivation. The association between miR-25 rs41274221 polymorphism and osteoporosis susceptibility is unknown. Herein, 300 patients with osteoporosis and 320 healthy controls were genotyped using polymerase chain reaction and Sanger sequencing to explore the role of miR-25 rs41274221 polymorphism in osteoporosis. The odds ratios (ORs) and 95% confidence intervals (CIs) were determined using logistic regression analysis. Additionally, this study also investigated the effect of miR-25 rs41274221 polymorphism on the expression of miR-25 and its target gene S1PR1 through luciferase reporter gene, qRT-PCR, and Western blot. The rs41274221 in miR-25 was found to be positively associated with osteoporosis and can be viewed as a protective factor. Furthermore, miR-25 rs41274221 polymorphism decreased the risk of osteoporosis among smokers. The TargetScan database predictions and dual-luciferase activity demonstrated that S1PR1 may be the target gene of miR-25. MiR-25 downregulated the S1PR1 mRNA and protein expressions. Patients with the AA genotype of rs41274221 polymorphism showed higher S1PR1 expression compared with the GG genotype. In conclusion, miR-25 rs41274221 polymorphism decreases the risk of osteoporosis through modifying the binding with S1PR1 and may serve as a novel biomarker for early diagnosis of osteoporosis. more...
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- 2023
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10. Non-invasive diagnostic potential of salivary miR-25-3p for periodontal disease and osteoporosis among a cohort of elderly patients with type 2 diabetes mellitus.
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Ni, Jing, Zhang, Qiong, and Lei, Fei
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PERIODONTAL disease diagnosis ,OSTEOPOROSIS diagnosis ,SALIVA analysis ,BIOMARKERS ,PERIODONTIUM ,MICRORNA ,TYPE 2 diabetes ,COMPARATIVE studies ,GENE expression profiling ,RESEARCH funding ,DESCRIPTIVE statistics ,BONE density ,POLYMERASE chain reaction ,LONGITUDINAL method ,DISEASE complications ,OLD age - Abstract
Objective: Osteoporosis (OP) and periodontal disease (PD) are two common health issues that threaten the older population and potentially connected each other in the context of type 2 diabetes mellitus (T2DM). Dysregulated expression of microRNAs (miRNAs) may contribute to the development and progression of both OP and PD among elderly T2DM patients. The present study aimed to evaluate the accuracy of miR-25-3p expression for the detection of OP and PD when compared to a mixed group of patients with T2DM. Methods: The study recruited 45 T2DM patients with normal bone mineral density (BMD) and healthy periodontium, 40 type 2 diabetic osteoporosis patients coexistent with PD, 50 type 2 diabetic osteoporosis patients with healthy periodontium, and 52 periodontally healthy individuals. miRNA expression measurements in the saliva were determined by real-time PCR. Results: The salivary expression of miR-25-3p was higher in type 2 diabetic osteoporosis patients than patients with T2DM only and healthy individuals (P < 0.05). Among type 2 diabetic osteoporosis patients, those with PD exhibited a higher salivary expression of miR-25-3p than those with healthy periodontium (P < 0.05). Among type 2 diabetic patients with healthy periodontium, a higher salivary expression of miR-25-3p was noted in those with OP than those without (P < 0.05). We also found a higher salivary expression of miR-25-3p in T2DM patients than healthy individuals (P < 0.05). It was revealed that the salivary expression of miR-25-3p was increased as the T scores of BMD of patients were lowered, the PPD and CAL values of patients were enhanced. The salivary expression of miR-25-3p used as a test to predict a diagnosis of PD among type 2 diabetic osteoporosis patients, a diagnosis of OP among type 2 diabetic patients, and a diagnosis of T2DM among healthy individuals produced AUC of 0.859. 0.824, and 0.886, respectively. Conclusion: The findings obtained from the study support salivary miR-25-3p confers non-invasive diagnostic potential for PD and OP among a cohort of elderly T2DM patients. [ABSTRACT FROM AUTHOR] more...
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- 2023
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11. Downregulation of miR-25-3p and Its Impact on PTAFR and IGF2BP3 Expression in Type 2 Diabetes Mellitus: Implications for Biomarker Discovery and Disease Pathogenesis.
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Rattanapan Y, Nongwa K, Supanpong C, Satsadeedat C, Sai-Ong T, Kooltheat N, and Chareonsirisuthigul T
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Background: This study is designed to investigate the differential microRNA (miRNA) expression profiles in individuals with and without type 2 diabetes mellitus (T2DM). The focus is on miRNAs that play a crucial role in the onset and progression of T2DM, particularly in glucose metabolism, inflammation, platelet reactivity, and endothelial dysfunction., Methods: Twenty samples were categorized into groups of T2DM and non-T2DM, and miRNA profiling was conducted using microarray analysis. The expression levels of the candidate miR-25-3p , as well as its target genes platelet-activating factor receptor ( PTAFR ) and insulin-like growth factor 2 mRNA binding protein 3 ( IGF2BP3 ), were validated using quantitative polymerase chain reaction (qPCR)., Results: The present study revealed a significant reduction in the level of miR-25-3p in the T2DM group compared to the non-T2DM group. This suggests higher levels of PTAFR and IGF2BP3 in individuals with T2DM, indicating a potential biomarker for the condition., Conclusions: The downregulation of miR-25-3p , which is associated with increased PTAFR levels, may contribute to heightened platelet reactivity and inflammation, worsening endothelial dysfunction, and potentially influencing vascular complications in diabetes. Additionally, the upregulation of IGF2BP3 is correlated with insulin resistance and β-cell dysfunction, which may contribute to elevated hyperglycemia and hyperinsulinemia, further aggravating the progression of diabetes. These findings highlight the potential of miR-25-3p and IGF2BP3 as biomarkers for T2DM and suggest their possible relevance for improving diagnosis and treatment strategies., Competing Interests: The authors disclose no conflict of interest., (Copyright 2024, Rattanapan et al.) more...
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- 2024
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12. miR-25-3p protects renal tubular epithelial cells from apoptosis induced by renal IRI by targeting DKK3
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Zhang Yu and Zuo Xiangrong
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mir-25-3p ,renal ischemia-reperfusion injury ,apoptosis ,dkk3 ,Biology (General) ,QH301-705.5 - Abstract
Renal ischemia-reperfusion injury (IRI) is one of the main causes of acute kidney injury (AKI). So far, there have been many studies on renal IRI, although an effective treatment method has not been developed. In recent years, growing evidence has shown that small noncoding RNAs play an important regulatory role in renal IRI. This article aims to explore whether microRNA-25-3p (miR-25-3p) plays a role in the molecular mechanism of renal IRI. The results showed that the expression level of miR-25-3p was significantly downregulated in a rat renal IRI model, and this result was confirmed with in vitro experiments. After the hypoxia-reoxygenation treatment, the apoptosis level of NRK-52E cells transfected with miR-25-3p mimics decreased significantly, and this antiapoptotic effect was antagonized by miR-25-3p inhibitors. In addition, we confirmed that DKK3 is a target of miR-25-3p. miR-25-3p exerts its protective effect against apoptosis on NRK-52E cells by inhibiting the expression of DKK3, and downregulating the expression level of miR-25-3p could disrupt this protective effect. In addition, we reconfirmed the role of miR-25-3p in rats. Therefore, we confirmed that miR-25-3p may target DKK3 to reduce renal cell damage caused by hypoxia and that miR-25-3p may be a new potential treatment for renal IRI. more...
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- 2021
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13. The Relationship and Expression of miR-451a , miR-25-3p and PTEN in Early Peritoneal Endometriotic Lesions and Their Modulation In Vitro.
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Nothnick, Warren B., Peterson, Riley, Minchella, Paige, Falcone, Tommaso, Graham, Amanda, and Findley, Austin
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Background: miR-451a can function as a tumor suppresser and has been shown to be elevated in both endometriotic lesion tissue and serum from women with endometriosis. To further explore the role of miR-451a in the pathophysiology of endometriosis, specifically, further evaluating its association with the tumor suppressor, phosphatase and tensin homolog (PTEN), we examined their expression in individual endometriotic lesion tissue to gain insight into their relationship and further explore if miR-451a regulates PTEN expression. Methods: A total of 55 red, peritoneal endometriotic lesions and matched eutopic endometrial specimens were obtained from 46 patients with endometriosis. miR-451a, miR-25-3p and PTEN mRNA levels were assessed by qRT-PCR and reported for each matched eutopic and ectopic sample. To evaluate miR-451a and miR-25-3p expression of miR-25-3p and PTEN, respectively, 12Z cells (endometriotic epithelial cell line) were transfected and miR-25-3p expression was assessed by qRT-PCR, while PTEN protein expression was assessed by Western blotting. Results: PTEN and miR-25-3p expression exhibited an inverse relationship, as did miR-25-3p and miR-451a in individual lesions. Over-expression of miR-451a in 12Z cells resulted in down-regulation of miR-25-3p, while up-regulation of miR-25-3p resulted in down-regulation of PTEN protein expression. Conclusions: By assessing individual endometriotic lesion expression, we discovered an inverse relationship between miR-451a, miR-25-3p and PTEN, while in vitro cell transfection studies suggest that miR-451a may regulate PTEN expression via modulating miR-25-3p. [ABSTRACT FROM AUTHOR] more...
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- 2022
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14. LncRNA CBR3-AS1 regulates of breast cancer drug sensitivity as a competing endogenous RNA through the JNK1/MEK4-mediated MAPK signal pathway
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Ming Zhang, Yan Wang, Longyang Jiang, Xinyue Song, Ang Zheng, Hua Gao, Minjie Wei, and Lin Zhao
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Chemoresistance ,Breast cancer ,CBR3-AS1 ,miR-25-3p ,MAPK signaling pathway ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Adriamycin (ADR) resistance is one of the main obstacles to improving the clinical prognosis of breast cancer patients. Long noncoding RNAs (lncRNAs) can regulate cell behavior, but the role of these RNAs in the anti-ADR activity of breast cancer remains unclear. Here, we aim to investigate the imbalance of a particular long noncoding RNA, lncRNA CBR3 antisense RNA 1 (CBR3-AS1), and its role in ADR resistance. Methods Microarray analysis of ADR-resistant breast cancer cells was performed to identify CBR3-AS1. CCK-8 and colony formation assays were used to detect the sensitivity of breast cancer cells to ADR. Dual-luciferase reporter, RNA pulldown, IHC and western blot analyses were used to verify the relationship between the expression of CBR3-AS1, miRNA and target genes. For in vivo experiments, the effect of CBR3-AS1 on breast cancer resistance was observed in a xenograft tumor model. The role of CBR3-AS1 in influencing ADR sensitivity was verified by clinical breast cancer specimens from the TCGA, CCLE, and GDSC databases. Results We found that CBR3-AS1 expression was significantly increased in breast cancer tissues and was closely correlated with poor prognosis. CBR3-AS1 overexpression promoted ADR resistance in breast cancer cells in vitro and in vivo. Mechanistically, we identified that CBR3-AS1 functioned as a competitive endogenous RNA by sponging miR-25-3p. MEK4 and JNK1 of the MAPK pathway were determined to be direct downstream proteins of the CBR3-AS1/miR-25-3p axis in breast cancer cells. Conclusions In summary, our findings demonstrate that CBR3-AS1 plays a critical role in the chemotherapy resistance of breast cancer by mediating the miR-25-3p and MEK4/JNK1 regulatory axes. The potential of CBR3-AS1 as a targetable oncogene and therapeutic biomarker of breast cancer was identified. more...
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- 2021
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15. MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma
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Rao H, Wu Z, Wei S, Jiang Y, Guo Q, Wang J, Chen C, and Yang H
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merlin ,mir-25-3p ,osteosarcoma ,proliferation ,apoptosis ,metastasis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Hua-chun Rao,1,* Zhao-ke Wu,1,* Si-da Wei,1 Yun Jiang,1 Qing-xin Guo,1 Jia-wen Wang,1 Chang-xian Chen,1 Hui-yong Yang2 1Quanzhou Orthopedic-Traumatological Hospital, Fengze District, Quanzhou, Fujian, People’s Republic of China; 2School of Medicine, Institute of Molecular Medicine, Huaqiao University, Quanzhou, People’s Republic of China*These authors contributed equally to this work.Correspondence: Chang-xian Chen Tel +86 13636913112Email ccx6070@qq.comHui-yong Yang Tel +86 15359531722Email shyhy@hqu.edu.cnPurpose: Moesin-ezrin-radixin-like protein (Merlin) has been identified as a tumor suppressor in several types of cancers. However, the biological function of Merlin in osteosarcoma remains unclear. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we sought to evaluate the regulation of Merlin expression by miR-25-3p and the role of the miR-25-3p/Merlin axis in osteosarcoma progression, with the aim of identifying a potential therapeutic target for osteosarcoma.Materials and Methods: TCGA (The Cancer Genome Atlas) database was used to analyze the correlation between Merlin expression and prognosis. RT-qPCR and Western blotting analyses were performed to compare Merlin expression between normal and malignant cells. A dual-luciferase reporter assay was performed to evaluate the direct targeting of Merlin by miR-25-3p. We overexpressed miR-25-3p, or/and Merlin, in U-2 OS and 143B cells, and studied their cellular functions in vitro. MTT and colony formation assays were performed to determine the effects on cell growth. EdU and cell cycle assays were performed to analyze the effects in cell replication. We used annexin V-fluorescein isothiocyanate and propidium iodide to stain apoptotic cells, and analyzed the cells using flow cytometry. The effects on cell metastasis were studied in wound healing and transwell assays. Lastly, the underlying mechanism was determined in RT-qPCR and Western blotting experiments.Results: Low Merlin expression was linked to poor prognosis. miR-25-3p was observed to directly target Merlin and downregulate its expression. miR-25-3p promoted cell growth, migration, and invasion, and inhibited apoptosis induced by cisplatin. Moreover, the overexpression of Merlin reversed the abovementioned effects of miR-25-3p. Further, the miR-25-3p/Merlin axis was observed to play an important role in the Hippo pathway, and regulated the expression of genes such as BIRC5, CTGF, and CYR61.Conclusion: miR-25-3p functions as an oncogenic microRNA in osteosarcoma by targeting Merlin, and may serve as a potential therapeutic target for osteosarcoma.Keywords: Merlin, miR-25-3p, osteosarcoma, proliferation, apoptosis, metastasis more...
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- 2020
16. LncRNA JPX promotes cervical cancer progression by modulating miR-25-3p/SOX4 axis
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Xia Chen, Jingxiu Yang, and Yuping Wang
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JPX ,miR-25-3p ,SOX4 ,Cervical cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Background The long noncoding RNA (lncRNA) JPX is a molecular switch for X-chromosome inactivation. Accumulating studies have shown that the aberrant expression and function of lncRNAs are involved in the occurrence and development of tumors. However, the functional importance and mechanism of the action of lncRNA JPX in cervical cancer (CC) remain unknown. Method In this study, qRT-PCR and western blotting were used to evaluate the mRNA or protein expression of JPX, miR-25-3p and SOX4 in CC tissues and cell lines. StarBase v2.0 database, luciferase reporter assay and RNA immunoprecipitation assay were used to explore the relationship between JPX and miR-25-3p. EdU assay, CCK-8 assay and transwell assay were utilized to evaluate the proliferation, migration and invasion of CC cells. The tumor xenograft assay in nude mice was performed to demonstrate the role of the JPX/miR-25-3p/SOX4 axis in CC. Results We found that JPX was markedly upregulated, whereas miR-25-3p was markedly downregulated in CC tissues and cell lines, and the expression of JPX was negatively correlated with miR-25-3p in CC tissues. Moreover, overexpression of JPX increased proliferation, migration and invasion of HeLa cells, whereas knockdown of JPX decreased proliferation, migration and invasion of HeLa cells. In contrast to JPX, overexpression of miR-25-3p decreased proliferation, migration and invasion of HeLa cells. In addition, knockdown of JPX was found to inhibit HeLa cell viability and tumor development via up-regulating the expression of miR-25-3p and inhibiting the expression of SOX4. Conclusions Our study demonstrates that JPX promotes cervical cancer progression through modulating the miR-25-3p/SOX4 axis, and may serve as a potential target for CC therapy. more...
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- 2020
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17. LncRNA SNHG12 alleviates hypertensive vascular endothelial injury through miR‐25‐3p/SIRT6 pathway.
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Qian, Wei, Zheng, Ze‐qi, Nie, Jun‐gang, Liu, Li‐juan, Meng, Xiang‐zhu, Sun, Hong, Xiao, Feng‐ming, and Kang, Ting
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LINCRNA ,HYPERTENSION ,REPORTER genes ,CASPASES ,WOUNDS & injuries - Abstract
The objective of this study was to find the role of LncRNA SNHG12 in the regulation of hypertensive vascular endothelial injury. LncRNA SNHG12 and miR‐25‐3p expression were detected by quantitative RT‐PCR. Protein levels of Sirtuin 6 (SIRT6), endothelial cell (EC) senescence markers p16 and p21, and EC marker CD31 were measured by Western blot. The apoptosis of HUVECs was detected by flow cytometry. The binding between LncRNA SNHG12 and miR‐25‐3p was verified by dual luciferase reporter gene assay and RNA pull‐down assay. As a result, LncRNA SNHG12 was down‐regulated in aortic primary ECs isolated from Ang II‐induced hypertensive mice and 1 kidney/deoxycorticosterone acetate/salt‐induced hypertensive mice. In Ang II‐treated HUVECs, the expression level of SNHG12 was reduced and the overexpression of SNHG12 inhibited EC senescence markers p16 and p21 expressions, the apoptosis of HUVECs, and caspase‐3 activity. Further investigation confirmed that LncRNA SNHG12 bound to miR‐25‐3p, and negatively regulated miR‐25‐3p expression. MiR‐25‐3p directly targeted SIRT6 and negatively regulated SIRT6 expression. In addition, SNHG12 overexpression inhibited Ang II‐induced HUVECs injury through regulating miR‐25‐3p. Finally, in vivo experiments showed LncRNA SNHG12 overexpression alleviated vascular endothelial injury in Ang II‐induced hypertensive mice. In conclusion, LncRNA SNHG12 alleviates vascular endothelial injury induced by hypertension through miR‐25‐3p/SIRT6 pathway. [ABSTRACT FROM AUTHOR] more...
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- 2021
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18. miR-25-3p promotes proliferation and inhibits autophagy of renal cells in polycystic kidney mice by regulating ATG14-Beclin 1
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Guojian Liu, Xiaowen Kang, Ping Guo, Yu Shang, Ruomei Du, Xiyue Wang, Liting Chen, Rui Yue, and Fanwu Kong
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mir-25-3p ,atg14 ,autophagy ,proliferation ,polycystic kidney disease ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
MicroRNAs are involved in the regulation of the autophagy and proliferation in several diseases. This study aims to verify the role of miR-25-3p in the proliferation and autophagy of renal cells in polycystic kidney disease (PKD). We found that kidney to body weight and blood urea content were increased in PKD mice. Cystic dilations were increased in kidney tissue from PKD mice, and autophagy-related protein ULK1 and the ratio of LC3-II/LC3-I were decreased, indicating autophagy was inhibited in PKD mice. In addition, miR-25-3p was upregulated in PKD mice, and inhibition of miR-25-3p decreased cystic dilations in kidney tissues, increased ULK1 expression and the ratio of LC3-II/LC3-I, indicating inhibition of miR-25-3p enhanced the autophagy in PKD. Besides, inhibition of miR-25-3p suppressed the proliferation of renal cells and downregulated E2F-1 and PCNA expressions. Importantly, miR-25-3p targetedly suppressed ATG14 expression in PKD cells. Finally, silencing ATG14 abolished the inhibition effect of miR-25-3p inhibitor on renal cell proliferation, and reversed the inhibition effect of miR-25-3p inhibitor on E2F-1 and PCNA expressions in in vitro and in vivo experiments, which suggested that ATG14 was involved in the regulation of miR-25-3p-mediated kidney cell proliferation. Therefore, inhibition of miR-25-3p promoted cell autophagy and suppressed cell proliferation in PKD mice through regulating ATG14. more...
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- 2020
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19. LncRNA FOXD2-AS1 Regulates miR-25-3p/Sema4c Axis To Promote The Invasion And Migration Of Colorectal Cancer Cells
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Zhang M, Jiang X, Jiang S, Guo Z, Zhou Q, and He J
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colorectal cancer ,foxd2-as1 ,mir-25-3p ,sema4c ,survival ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Mengyan Zhang,1,* Xiang Jiang,2,* Sumei Jiang,3 Zhongying Guo,4 Qinfeng Zhou,5 Jingdong He1 1Department of Oncology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an City, Jiangsu Province 223300, People’s Republic of China; 2Courage Pancreas Surgical, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an City, Jiangsu Province 223300, People’s Republic of China; 3Ultrasonic Department, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an City, Jiangsu Province 223300, People’s Republic of China; 4Department of Pathology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an City, Jiangsu Province 223300, People’s Republic of China; 5Department of Laboratory Medicine, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 215600, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingdong HeDepartment Of Oncology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, No. 6 Beijing West Road, Huaiyin District, Huai’an City, Jiangsu Province 223300, People’s Republic of ChinaTel +86-0517-84907287Email hejingdong66@yeah.netPurpose: Although the roles of lncRNA FOXD2-AS1 have been investigated in many types of cancers including colorectal cancer (CRC), its functionality remains to be further investigated. Analysis of the TCGA data set revealed that FOXD2-AS1 was up-regulated in CRC tissues. This study aimed to analyze the function of FOXD2-AS1 in CRC.Methods: FOXD2-AS1 expression was detected by qPCR. A 5-year follow-up study was performed to analyze the prognostic value of FOXD2-AS1 for CRC. Overexpression experiments were performed to analyze the interactions among FOXD2-AS1, miR-25-3p and Sema4C. Transwell assays were performed to analyze cell invasion and migration.Results: In this study, we further confirmed the up-regulation of FOXD2-AS1 in CRC patients and showed that high FOXD2-AS1 level predicted poor survival. Bioinformatics analysis showed that miR-25-3p may bind FOXD2-AS1, while over-expression experiments showed no effects on each other’s expression. Instead, FOXD2-AS1 over-expression led to the up-regulate Sema4C, which is a target of miR-25-3p. Transwell assay showed that FOXD2-AS1 and Sema4C over-expression led to the increased invasion and migration rates of CRC cells. MiR-25-3p plays the opposite role and attenuated the effects of FOXD2-AS1 and Sema4C over-expression.Conclusion: FOXD2-AS1 may regulate the miR-25-3p/Sema4C axis to promote the invasion and migration of CRC cells.Keywords: colorectal cancer, FOXD2-AS1, miR-25-3p, Sema4C, survival more...
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- 2019
20. ACOX1, regulated by C/EBPα and miR-25-3p, promotes bovine preadipocyte adipogenesis.
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Feng Zhang, Qi Xiong, Hu Tao, Yang Liu, Nian Zhang, Xiao-Feng Li, Xiao-Jun Suo, Qian-Ping Yang, and Ming-Xin Chen
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ADIPOGENESIS , *BOS , *SITE-specific mutagenesis , *BEEF cattle , *MEAT quality , *FATTY acids - Abstract
Acyl-coenzyme A oxidase 1 (ACOX1) is the first and rate-limiting enzyme in peroxisomal fatty acid β-oxidation of fatty acids. Previous studies have reported that ACOX1 was correlated with the meat quality of livestock, while the role of ACOX1 in intramuscular adipogenesis of beef cattle and its transcriptional and post-transcriptional regulatory mechanisms remain unclear. In the present study, gain-of-function and loss-of-function assays demonstrated that ACOX1 positively regulated the adipogenesis of bovine intramuscular preadipocytes. The C/EBPα-binding sites in the bovine ACOX1 promoter region at -1142 to -1129 bp, -831 to -826 bp, and -303 to -298 bp were identified by promoter deletion analysis and site-directed mutagenesis. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) further showed that these three regions are C/EBPα-binding sites, both in vitro and in vivo, indicating that C/EBPα directly interacts with the bovine ACOX1 promoter and inhibits its transcription. Furthermore, the results from bioinformatics analysis, dual luciferase assay, site-directed mutagenesis, qRT-PCR, and Western blotting demonstrated that miR-25-3p directly targeted the ACOX1 3'UTR (3'UTR). Taken together, our findings suggest that ACOX1, regulated by transcription factor C/EBPα and miR-25-3p, promotes adipogenesis of bovine intramuscular preadipocytes via regulating peroxisomal fatty acid β-oxidation. [ABSTRACT FROM AUTHOR] more...
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- 2021
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21. A feature-based analysis identifies COL1A2 as a regulator in pancreatic cancer
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Jie Wu, Jing Liu, XiaoQing Wei, Qi Yu, XiangHuan Niu, ShuHong Tang, and Lei Song
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pancreatic cancer ,col1a2 ,mir-25-3p ,bioinformatics ,Therapeutics. Pharmacology ,RM1-950 - Abstract
This study aimed to identify genetic biomarkers in pancreatic cancer (PC) and explore its function in PC via a feature-base analysis of bioinformatics. OMIM and DisGeNET databases discovered 209 PC connected genes and then 516 connected genes were identified. We selected 29 genes according to optimal features and chose COL1A2, which had the highest expression, for the following experiment. The expression of COL1A2 was determined by qRT-PCR; cell proliferation was determined by MTT assay; migration and invasion after COL1A2 and miR-25-3p transfection was evaluated by Transwell assay. COL1A2 presented the highest expression in PC tissues, which was validated in functional experiments. MiR-25-3p suppressed the expression of COL1A2 in cell lines and inhibited migration, invasion and proliferation of PC cells. MiR-25-3p could suppress the expression of COL1A2 and inhibit the proliferation, migration and invasion of PC cells which provided a new idea for the detection and treatment of PC. more...
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- 2019
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22. LncRNA CBR3-AS1 regulates of breast cancer drug sensitivity as a competing endogenous RNA through the JNK1/MEK4-mediated MAPK signal pathway.
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Zhang, Ming, Wang, Yan, Jiang, Longyang, Song, Xinyue, Zheng, Ang, Gao, Hua, Wei, Minjie, and Zhao, Lin
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BREAST cancer ,LINCRNA ,ANTINEOPLASTIC agents ,MITOGEN-activated protein kinases ,WESTERN immunoblotting - Abstract
Background: Adriamycin (ADR) resistance is one of the main obstacles to improving the clinical prognosis of breast cancer patients. Long noncoding RNAs (lncRNAs) can regulate cell behavior, but the role of these RNAs in the anti-ADR activity of breast cancer remains unclear. Here, we aim to investigate the imbalance of a particular long noncoding RNA, lncRNA CBR3 antisense RNA 1 (CBR3-AS1), and its role in ADR resistance. Methods: Microarray analysis of ADR-resistant breast cancer cells was performed to identify CBR3-AS1. CCK-8 and colony formation assays were used to detect the sensitivity of breast cancer cells to ADR. Dual-luciferase reporter, RNA pulldown, IHC and western blot analyses were used to verify the relationship between the expression of CBR3-AS1, miRNA and target genes. For in vivo experiments, the effect of CBR3-AS1 on breast cancer resistance was observed in a xenograft tumor model. The role of CBR3-AS1 in influencing ADR sensitivity was verified by clinical breast cancer specimens from the TCGA, CCLE, and GDSC databases. Results: We found that CBR3-AS1 expression was significantly increased in breast cancer tissues and was closely correlated with poor prognosis. CBR3-AS1 overexpression promoted ADR resistance in breast cancer cells in vitro and in vivo. Mechanistically, we identified that CBR3-AS1 functioned as a competitive endogenous RNA by sponging miR-25-3p. MEK4 and JNK1 of the MAPK pathway were determined to be direct downstream proteins of the CBR3-AS1/miR-25-3p axis in breast cancer cells. Conclusions: In summary, our findings demonstrate that CBR3-AS1 plays a critical role in the chemotherapy resistance of breast cancer by mediating the miR-25-3p and MEK4/JNK1 regulatory axes. The potential of CBR3-AS1 as a targetable oncogene and therapeutic biomarker of breast cancer was identified. [ABSTRACT FROM AUTHOR] more...
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- 2021
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23. Potential of miR-25-3p in protection of chondrocytes: emphasis on osteoarthritis.
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Xiao He and Lili Deng
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CARTILAGE cells ,BIOLOGICAL models ,REVERSE transcriptase polymerase chain reaction ,FLOW cytometry ,ANIMAL experimentation ,WESTERN immunoblotting ,MICRORNA ,APOPTOSIS ,RATS ,GENE expression ,CELL survival ,OSTEOARTHRITIS ,CELL proliferation ,TUMOR necrosis factors ,POLYMERASE chain reaction ,BIOLOGICAL assay ,CARRIER proteins - Abstract
Introduction. Osteoarthritis (OA) is the most prevailing musculoskeletal dysfunction triggered by lesions in synovial membranes and articular cartilage. MicroRNAs (miRNAs) have emerged as crucial regulators participated in many biological processes, such as osteoarthritis. This study was undertaken to address the role of miR-25-3p in the apoptosis of rat chondrocytes under an OA-like condition and its underlying mechanism. Material and methods. OA cellular model was established in rat chondrocytes by TNF-a induction. Then, qRTPCR and Western blotting were utilized for evaluation of the expressions of miR-25-3p and insulin-like growth factor-binding protein 7 (IGFBP7), CCK-8 assay for inspection of chondrocyte viability, flow cytometry for assessment of cell apoptosis rate, Western blotting for the detection of cleaved caspase-3 level and dual-luciferase reporter gene assay for verification of the targeting relationship between miR-25-3p and IGFBP7. Results. The miR-25-3p expression was decreased and IGFBP7 was elevated in TNF-a-induced rat chondrocytes. The miR-25-3p inhibited chondrocyte apoptosis and IGFBP7 promoted apoptosis as evidenced by enhanced cell viability and suppressed cell apoptosis in OA chondrocytes after miR-25-3p overexpression or IGFBP7 knockdown. The miR-25-3p facilitated chondrocyte viability and repressed cell apoptosis in OA by negatively regulating IGFBP7. Conclusions. MiR-25-3p negatively regulates IGFBP7 to promote chondrocyte proliferation and restrain chondrocyte apoptosis. Our findings suggest that the regulation of IGFBP7 by miR-25-3p may emerge as a novel therapeutic regimen for OA. [ABSTRACT FROM AUTHOR] more...
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- 2021
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24. miR-25-3p promotes proliferation and inhibits autophagy of renal cells in polycystic kidney mice by regulating ATG14-Beclin 1.
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Liu, Guojian, Kang, Xiaowen, Guo, Ping, Shang, Yu, Du, Ruomei, Wang, Xiyue, Chen, Liting, Yue, Rui, and Kong, Fanwu
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POLYCYSTIC kidney disease ,AUTOPHAGY ,CYSTIC kidney disease ,MICE ,CELL proliferation - Abstract
MicroRNAs are involved in the regulation of the autophagy and proliferation in several diseases. This study aims to verify the role of miR-25-3p in the proliferation and autophagy of renal cells in polycystic kidney disease (PKD). We found that kidney to body weight and blood urea content were increased in PKD mice. Cystic dilations were increased in kidney tissue from PKD mice, and autophagy-related protein ULK1 and the ratio of LC3-II/LC3-I were decreased, indicating autophagy was inhibited in PKD mice. In addition, miR-25-3p was upregulated in PKD mice, and inhibition of miR-25-3p decreased cystic dilations in kidney tissues, increased ULK1 expression and the ratio of LC3-II/LC3-I, indicating inhibition of miR-25-3p enhanced the autophagy in PKD. Besides, inhibition of miR-25-3p suppressed the proliferation of renal cells and downregulated E2F-1 and PCNA expressions. Importantly, miR-25-3p targetedly suppressed ATG14 expression in PKD cells. Finally, silencing ATG14 abolished the inhibition effect of miR-25-3p inhibitor on renal cell proliferation, and reversed the inhibition effect of miR-25-3p inhibitor on E2F-1 and PCNA expressions in in vitro and in vivo experiments, which suggested that ATG14 was involved in the regulation of miR-25-3p-mediated kidney cell proliferation. Therefore, inhibition of miR-25-3p promoted cell autophagy and suppressed cell proliferation in PKD mice through regulating ATG14. [ABSTRACT FROM AUTHOR] more...
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- 2020
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25. LncRNA JPX promotes cervical cancer progression by modulating miR-25-3p/SOX4 axis.
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Chen, Xia, Yang, Jingxiu, and Wang, Yuping
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CERVICAL cancer ,CANCER invasiveness ,HELA cells ,NON-coding RNA ,MOLECULAR switches - Abstract
Background: The long noncoding RNA (lncRNA) JPX is a molecular switch for X-chromosome inactivation. Accumulating studies have shown that the aberrant expression and function of lncRNAs are involved in the occurrence and development of tumors. However, the functional importance and mechanism of the action of lncRNA JPX in cervical cancer (CC) remain unknown. Method: In this study, qRT-PCR and western blotting were used to evaluate the mRNA or protein expression of JPX, miR-25-3p and SOX4 in CC tissues and cell lines. StarBase v2.0 database, luciferase reporter assay and RNA immunoprecipitation assay were used to explore the relationship between JPX and miR-25-3p. EdU assay, CCK-8 assay and transwell assay were utilized to evaluate the proliferation, migration and invasion of CC cells. The tumor xenograft assay in nude mice was performed to demonstrate the role of the JPX/miR-25-3p/SOX4 axis in CC. Results: We found that JPX was markedly upregulated, whereas miR-25-3p was markedly downregulated in CC tissues and cell lines, and the expression of JPX was negatively correlated with miR-25-3p in CC tissues. Moreover, overexpression of JPX increased proliferation, migration and invasion of HeLa cells, whereas knockdown of JPX decreased proliferation, migration and invasion of HeLa cells. In contrast to JPX, overexpression of miR-25-3p decreased proliferation, migration and invasion of HeLa cells. In addition, knockdown of JPX was found to inhibit HeLa cell viability and tumor development via up-regulating the expression of miR-25-3p and inhibiting the expression of SOX4. Conclusions: Our study demonstrates that JPX promotes cervical cancer progression through modulating the miR-25-3p/SOX4 axis, and may serve as a potential target for CC therapy. [ABSTRACT FROM AUTHOR] more...
- Published
- 2020
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26. Exosomes secreted by chronic hepatitis B patients with PNALT and liver inflammation grade ≥ A2 promoted the progression of liver cancer by transferring miR‐25‐3p to inhibit the co‐expression of TCF21 and HHIP.
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Ouyang, Yi, Tang, Yujing, Fu, Lei, Peng, Shifang, Wu, Wanfeng, Tan, Deming, and Fu, Xiaoyu
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EXOSOMES , *LIVER cancer , *HEPATITIS , *CANCER invasiveness , *CHRONIC hepatitis B , *CELL proliferation , *CELL survival - Abstract
Objectives: The current study aimed to investigate the mechanism by which exosomes secreted by CHB patients with PNALT and liver inflammation grade (≥A2) affected the development of liver cancer. Materials and methods: Gene expression was assessed by RT‐PCR, Western blotting and immunohistochemistry. CCK‐8, colony formation, transwell, scratch‐wound and flow cytometry assays were used to detect cell viability, proliferation, apoptosis and metastasis. The interaction of TCF21 and HHIP was assessed by co‐immunoprecipitation assay. Luciferase reporter was used to detect the combination of TCF21/HHIP and miR‐25‐3p. Xenograft studies in nude mice manifested tumour growth ability of miR‐25‐3p. Bioinformatics analyses were conducted using TargetScan, EVmiRNA, TCGA, GEO, DAVID, COEXPEDIA, UALCAN, UCSC and the Human Protein Atlas databases. Results: CHB‐PNALT‐Exo (≥A2) promoted the proliferation and metastasis of HepG2.2.15 cells. miR‐25‐3p was upregulated in CHB‐PNALT‐Exo (≥A2). miR‐25‐3p overexpression promoted cell proliferation and metastasis and was related to poor survival in patients with CHB‐PNALT (≥A2). The cell proliferation‐ and metastasis‐promoting functions of CHB‐PNALT‐Exo (≥A2) were abolished by miR‐25‐3p inhibitors. TCF21 directly interacted with HHIP. Inhibition of TCF21 or HHIP promoted cell proliferation and metastasis. Knockdown of TCF21 or HHIP counteracted the effects of CHB‐PNALT‐Exo (≥A2) containing miR‐25‐3p inhibitor on cell proliferation, metastasis and the expression of Ki67, E‐cadherin and caspase‐3/‐9. Conclusions: Transfer of miR‐25‐3p by CHB‐PNALT‐Exo promoted the development of liver cancer by inhibiting the co‐expression of TCF21 and HHIP. [ABSTRACT FROM AUTHOR] more...
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- 2020
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27. Hsa_circ_0043265 Suppresses Proliferation, Metastasis, EMT and Promotes Apoptosis in Non-Small Cell Lung Cancer Through miR-25-3p/FOXP2 Pathway.
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Ren, Tiejun, Liu, Chang, Hou, Jianfeng, and Shan, Fengxiao
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NON-small-cell lung carcinoma , *LUCIFERASES , *EPITHELIAL-mesenchymal transition , *CIRCULAR RNA - Abstract
Purpose: Non-small cell lung cancer (NSCLC) is the largest type of lung cancer (LC) with a higher mortality rate. Circular RNAs (circRNAs) have been shown to play an important role in cancer progression. Therefore, this study was to explore the function of hsa_circ_0043265 in NSCLC. Methods: The expression levels of hsa_circ_0043265, microRNA-25-3p (miR-25-3p) and forkhead box P2 (FOXP2) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Ribonuclease R (RNase R) and Actinomycin D (ActD) were used to verify the authenticity and stability of hsa_circ_0043265. Cell counting kit-8 (CCK-8), flow cytometry and transwell assays were used to evaluate the abilities of proliferation, apoptosis, migration and invasion of NSCLC cells. Also, Western blot (WB) analysis was performed to assess the levels of apoptosis, epithelial–mesenchymal transition (EMT) and proliferation-related proteins and FOXP2 protein. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were used to verify the interaction between miR-25-3p and hsa_circ_0043265 or FOXP2. Besides, mice xenograft models were constructed to confirm the effect of hsa_circ_0043265 on NSCLC tumor growth in vivo. Results: Hsa_circ_0043265 was lowly expressed in NSCLC tissues and cells, and its overexpression inhibited the proliferation, migration, invasion and EMT process, while improved the apoptosis of NSCLC cells. MiR-25-3p could be sponged by hsa_circ_0043265, and its overexpression could invert the suppression effect of overexpressed-hsa_circ_0043265 on NSCLC progression. Moreover, FOXP2 was a target of miR-25-3p, and its silencing also could reverse the inhibition effect of overexpressed-hsa_circ_0043265 on NSCLC progression. In addition, hsa_circ_0043265 overexpression reduced the tumor growth of NSCLC in vivo. Conclusion: Hsa_circ_0043265 could sponge miR-25-3p to improve FOXP2 expression, thereby inhibiting NSCLC progression. This study showed that hsa_circ_0043265 could be a potential biomarker for early diagnosis of NSCLC. [ABSTRACT FROM AUTHOR] more...
- Published
- 2020
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28. MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2
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Hua Chen, Hong Pan, Yi Qian, Wenbin Zhou, and Xiaoan Liu
- Subjects
TNBC ,miR-25-3p ,Proliferation ,BTG2 ,AKT ,ERK ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Triple-negative breast cancer (TNBC) is highly invasive and aggressive and lacks specific molecular targets to improve the prognosis. MiR-25-3p promotes proliferation of many tumors and its role and underlying mechanisms in TNBC remain to be well elucidated. Methods Differential expression of miR-25-3p in TNBC was measured with quantitative real-time PCR (qRT-PCR) in both TNBC tissues and cell lines and was validated in the Cancer Genome Atlas (TCGA) database. The effects of miR-25-3p on proliferation, apoptosis capacity of TNBC were evaluated using Cell counting kit-8 (CCK-8), colony formation assay and Annexin V-FITC/PI analyses. The tumor growth in vivo was observed in xenograft model. Luciferase reporter assay, qPCR and western blot were performed to validate a potential target of miR-25-3p in TNBC. Involvement of the AKT and MAPK pathways was investigated by western blot. Results MiR-25-3p was found to be upregulated in TNBC in tissues and cell lines. MiR-25-3p promoted TNBC cell proliferation in vitro and tumor growth in xenograft model, while suppression of miR-25-3p induced cell apoptosis. The luciferase reporter assay confirmed that B-cell translocation gene 2 (BTG2) might be a direct target of miR-25-3p, and its expression was negatively regulated by miR-25-3p. Moreover, inhibition of BTG2 expression accounted for the role of miR-25-3p in TNBC. Furthermore, BTG2 suppression might indirectly activate the AKT and ERK-MAPK signaling pathways to mediate the downstream effects of miR-25-3p. Conclusions This study demonstrates that miR-25-3p promotes proliferation by targeting tumor suppressor BTG2 and may identify new diagnostic and therapeutic targets in TNBC. more...
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- 2018
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29. A feature-based analysis identifies COL1A2 as a regulator in pancreatic cancer.
- Author
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Wu, Jie, Liu, Jing, Wei, XiaoQing, Yu, Qi, Niu, XiangHuan, Tang, ShuHong, and Song, Lei
- Subjects
PANCREATIC cancer ,CELL proliferation ,CELL lines ,GENE transfection - Abstract
This study aimed to identify genetic biomarkers in pancreatic cancer (PC) and explore its function in PC via a feature-base analysis of bioinformatics. OMIM and DisGeNET databases discovered 209 PC connected genes and then 516 connected genes were identified. We selected 29 genes according to optimal features and chose COL1A2, which had the highest expression, for the following experiment. The expression of COL1A2 was determined by qRT-PCR; cell proliferation was determined by MTT assay; migration and invasion after COL1A2 and miR-25-3p transfection was evaluated by Transwell assay. COL1A2 presented the highest expression in PC tissues, which was validated in functional experiments. MiR-25-3p suppressed the expression of COL1A2 in cell lines and inhibited migration, invasion and proliferation of PC cells. MiR-25-3p could suppress the expression of COL1A2 and inhibit the proliferation, migration and invasion of PC cells which provided a new idea for the detection and treatment of PC. [ABSTRACT FROM AUTHOR] more...
- Published
- 2019
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30. LncRNA OIP5-AS1 accelerates intervertebral disc degeneration by targeting miR-25-3p
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Zhaoping Che, Jie Xueqin, and Zongyu Zhang
- Subjects
Inflammation ,Lipopolysaccharides ,Male ,Nucleus Pulposus ,Base Sequence ,intervertebral disc degeneration ,Apoptosis ,Bioengineering ,General Medicine ,Middle Aged ,Applied Microbiology and Biotechnology ,Extracellular Matrix ,Up-Regulation ,MicroRNAs ,nucleus pulposus cells ,Humans ,Female ,RNA, Long Noncoding ,oip5-as1 ,mir-25-3p ,TP248.13-248.65 ,Research Article ,Research Paper ,Cell Proliferation ,Biotechnology - Abstract
It is obvious that epigenetic processes influence the evolution of intervertebral disc degeneration (IDD). However, its molecular mechanisms are poorly understood. Long noncoding RNAs (lncRNAs) have been validated to exert vital roles in IDD. Therefore, we tested the hypothesis that OIP5-AS1, a potential regulator of IDD, modulates IDD progression. RT-PCR was utilized to detect levels of OIP5-AS1, miR-25-3p, Collagen II and Aggrecan in IDD tissues and nucleus pulposus cells (NPCs). Immunofluorescence assay measured Collagen II expression. CCK-8, EdU, and flow cytometry estimated the levels of proliferation and apoptosis. Proteins were assessed via Western blot. The binding affinity of OIP5-AS1 with miR-25-3p was investigated by luciferase reporter assay. Enzyme-linked immunosorbent assay (ELISA) analyzed the levels of inflammatory factors. OIP5-AS1 was high expressed in IDD tissues and its expression gradually promoted with the increasing of Pfirrmann scores. The cell morphology of NPCs changed into spindle-shaped, and Collagen II expression was low. After OIP5-AS1 was silenced, cell proliferation was boosted whereas both apoptosis and extracellular matrix (ECM) degradation were restrained. In LPS-activated NPCs, OIP5-AS1 depletion also suppressed inflammation response. Further, miR-25-3p was a target of OIP5-AS1. The effects of OIP5-AS1 silence on proliferation, apoptosis, and ECM degradation were reversed upon miR-25-3p downregulation. Moreover, the inhibitory impact of OIP5-AS1 knockdown on the inflammation of LPS-treated NPCs was rescued with miR-25-3p inference. In general, lncRNA OIP5-AS1 exerted its effects in IDD by targeting miR-25-3p, implying the usage of OIP5-AS1/miR-25-3p as a novel regulatory axis for the molecular targets of IDD therapy. more...
- Published
- 2021
31. Retraction: MiR-25-3p targets PTEN to regulate the migration, invasion, and apoptosis of esophageal cancer cells via the PI3K/AKT pathway.
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- 2024
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32. miR-25-3p, Positively Regulated by Transcription Factor AP-2α, Regulates the Metabolism of C2C12 Cells by Targeting Akt1.
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Zhang, Feng, Chen, Kun, Tao, Hu, Kang, Tingting, Xiong, Qi, Zeng, Qianhui, Liu, Yang, Jiang, Siwen, and Chen, Mingxin
- Subjects
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MICRORNA , *CELL metabolism , *ACTIVATOR protein-2 transcription factors , *PROTEIN kinases , *CELL physiology - Abstract
MiR-25, a member of the miR-106b-25 cluster, has been reported as playing an important role in many biological processes by numerous studies, while the role of miR-25 in metabolism and its transcriptional regulation mechanism remain unclear. In this study, gain-of-function and loss-of-function assays demonstrated that miR-25-3p positively regulated the metabolism of C2C12 cells by attenuating phosphoinositide 3-kinase (PI3K) gene expression and triglyceride (TG) content, and enhancing the content of adenosine triphosphate (ATP) and reactive oxygen species (ROS). Furthermore, the results from bioinformatics analysis, dual luciferase assay, site-directed mutagenesis, qRT-PCR, and Western blotting demonstrated that miR-25-3p directly targeted the AKT serine/threonine kinase 1 (Akt1) 3' untranslated region (30UTR). The core promoter of miR-25-3p was identified, and the transcription factor activator protein-2α (AP-2α) significantly increased the expression of mature miR-25-3p by binding to its core promoter in vivo, as indicated by the chromatin immunoprecipitation (ChIP) assay, and AP-2α binding also downregulated the expression of Akt1. Taken together, our findings suggest that miR-25-3p, positively regulated by the transcription factor AP-2α, enhances C2C12 cell metabolism by targeting the Akt1 gene. [ABSTRACT FROM AUTHOR] more...
- Published
- 2018
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33. ACOX1, regulated by C/EBPα and miR-25-3p, promotes bovine preadipocyte adipogenesis
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Hu Tao, Li Xiaofeng, Qi Xiong, Suo Xiaojun, Feng Zhang, Mingxin Chen, Yang Qianping, Yang Liu, and Zhang Nian
- Subjects
Male ,0301 basic medicine ,Transcription, Genetic ,Down-Regulation ,030209 endocrinology & metabolism ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Adipocytes ,CCAAT-Enhancer-Binding Protein-alpha ,Animals ,Luciferase ,Promoter Regions, Genetic ,3' Untranslated Regions ,Molecular Biology ,Transcription factor ,chemistry.chemical_classification ,Adipogenesis ,Base Sequence ,Chemistry ,Research ,bovine ,CEBPα ,Fatty acid ,Promoter ,Peroxisome ,Molecular biology ,MicroRNAs ,030104 developmental biology ,miR-25-3p ,ACOX1 ,Cattle ,Acyl-CoA Oxidase ,Chromatin immunoprecipitation ,Protein Binding - Abstract
Acyl-coenzyme A oxidase 1 (ACOX1) is the first and rate-limiting enzyme in peroxisomal fatty acid β-oxidation of fatty acids. Previous studies have reported that ACOX1 was correlated with the meat quality of livestock, while the role of ACOX1 in intramuscular adipogenesis of beef cattle and its transcriptional and post-transcriptional regulatory mechanisms remain unclear. In the present study, gain-of-function and loss-of-function assays demonstrated that ACOX1 positively regulated the adipogenesis of bovine intramuscular preadipocytes. The C/EBPα-binding sites in the bovine ACOX1 promoter region at −1142 to −1129 bp, −831 to −826 bp, and −303 to −298 bp were identified by promoter deletion analysis and site-directed mutagenesis. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) further showed that these three regions are C/EBPα-binding sites, both in vitro and in vivo, indicating that C/EBPα directly interacts with the bovine ACOX1 promoter and inhibits its transcription. Furthermore, the results from bioinformatics analysis, dual luciferase assay, site-directed mutagenesis, qRT-PCR, and Western blotting demonstrated that miR-25-3p directly targeted the ACOX1 3’UTR (3’UTR). Taken together, our findings suggest that ACOX1, regulated by transcription factor C/EBPα and miR-25-3p, promotes adipogenesis of bovine intramuscular preadipocytes via regulating peroxisomal fatty acid β-oxidation. more...
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- 2021
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34. MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2.
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Chen, Hua, Pan, Hong, Qian, Yi, Zhou, Wenbin, and Liu, Xiaoan
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TRIPLE-negative breast cancer ,MICRORNA ,CANCER cell proliferation ,B cells ,APOPTOSIS ,TUMOR growth ,XENOGRAFTS - Abstract
Background: Triple-negative breast cancer (TNBC) is highly invasive and aggressive and lacks specific molecular targets to improve the prognosis. MiR-25-3p promotes proliferation of many tumors and its role and underlying mechanisms in TNBC remain to be well elucidated. Methods: Differential expression of miR-25-3p in TNBC was measured with quantitative real-time PCR (qRT-PCR) in both TNBC tissues and cell lines and was validated in the Cancer Genome Atlas (TCGA) database. The effects of miR-25-3p on proliferation, apoptosis capacity of TNBC were evaluated using Cell counting kit-8 (CCK-8), colony formation assay and Annexin V-FITC/PI analyses. The tumor growth in vivo was observed in xenograft model. Luciferase reporter assay, qPCR and western blot were performed to validate a potential target of miR-25-3p in TNBC. Involvement of the AKT and MAPK pathways was investigated by western blot. Results: MiR-25-3p was found to be upregulated in TNBC in tissues and cell lines. MiR-25-3p promoted TNBC cell proliferation in vitro and tumor growth in xenograft model, while suppression of miR-25-3p induced cell apoptosis. The luciferase reporter assay confirmed that B-cell translocation gene 2 (BTG2) might be a direct target of miR-25-3p, and its expression was negatively regulated by miR-25-3p. Moreover, inhibition of BTG2 expression accounted for the role of miR-25-3p in TNBC. Furthermore, BTG2 suppression might indirectly activate the AKT and ERK-MAPK signaling pathways to mediate the downstream effects of miR-25-3p. Conclusions: This study demonstrates that miR-25-3p promotes proliferation by targeting tumor suppressor BTG2 and may identify new diagnostic and therapeutic targets in TNBC. [ABSTRACT FROM AUTHOR] more...
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- 2018
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35. A functional polymorphism at the miR-25-3p binding site in the 3′-untranslated region of the S1PR1 gene decreases the risk of osteoporosis in Chinese postmenopausal women.
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Yang, Haoyu, Xiong, Chenwei, Yu, Zhentang, Yang, Zhicheng, Zhang, Yi, Zhang, Junjie, Huang, Yong, Xu, Nanwei, Zhou, Xindie, Jiang, Mengqing, and Xu, Zhonghua
- Abstract
[Display omitted] The low bone mineral density due to abnormally activated osteoclasts can induce bone disorders such as osteopenia and osteoporosis. MiR-25-3p modulates sphingosine-1-phosphate receptor 1 (S1PR1) expression to enhance osteoclast motivation. The association between miR-25 rs41274221 polymorphism and osteoporosis susceptibility is unknown. Herein, 300 patients with osteoporosis and 320 healthy controls were genotyped using polymerase chain reaction and Sanger sequencing to explore the role of miR-25 rs41274221 polymorphism in osteoporosis. The odds ratios (ORs) and 95% confidence intervals (CIs) were determined using logistic regression analysis. Additionally, this study also investigated the effect of miR-25 rs41274221 polymorphism on the expression of miR-25 and its target gene S1PR1 through luciferase reporter gene, qRT-PCR, and Western blot. The rs41274221 in miR-25 was found to be positively associated with osteoporosis and can be viewed as a protective factor. Furthermore, miR-25 rs41274221 polymorphism decreased the risk of osteoporosis among smokers. The TargetScan database predictions and dual-luciferase activity demonstrated that S1PR1 may be the target gene of miR-25. MiR-25 downregulated the S1PR1 mRNA and protein expressions. Patients with the AA genotype of rs41274221 polymorphism showed higher S1PR1 expression compared with the GG genotype. In conclusion, miR-25 rs41274221 polymorphism decreases the risk of osteoporosis through modifying the binding with S1PR1 and may serve as a novel biomarker for early diagnosis of osteoporosis. [ABSTRACT FROM AUTHOR] more...
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- 2023
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36. MicroRNA-25-3p promotes cisplatin resistance in Non-small-cell lung carcinoma (NSCLC) through adjusting PTEN/PI3K/AKT route
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Nanjun Hu, Jun Li, Kang Chen, Dan Cong, and Butong Sun
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Lung Neoplasms ,Mice, Nude ,Bioengineering ,Drug resistance ,Applied Microbiology and Biotechnology ,Mice ,Phosphatidylinositol 3-Kinases ,In vivo ,Annexin ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,microRNA ,Animals ,Humans ,pten/pi3k/akt ,PTEN ,mir-25-3p ,Protein kinase B ,PI3K/AKT/mTOR pathway ,biology ,Cell growth ,Chemistry ,PTEN Phosphohydrolase ,General Medicine ,MicroRNAs ,A549 Cells ,Drug Resistance, Neoplasm ,biology.protein ,Cancer research ,Cisplatin ,cisplatin resistance ,Proto-Oncogene Proteins c-akt ,nsclc ,TP248.13-248.65 ,Research Article ,Research Paper ,Signal Transduction ,Biotechnology - Abstract
MicroRNAs exert crucial effects in the drug resistance. The purpose of this research was to investigate the miR-25-3p effects on DDP resistance in NSCLC. We used RT-qPCR to evaluate the expression of miR-25-3p. Cell growth was determined using MTS assay. Cellular bio-activity was analyzed via Colony formation, Annexin V/PI, and Transwell assay. Luciferase reporter assay was used to determine miR-25-3p and PTEN binding. Western blot was used to determine PTEN, PI3K, p-AKT/AKT expression. In-vivo study was used to determine the effects of miR-25-3p on the tumor growth. Expression of miR-25-3p is increased in NSCLC cisplatin resistant A549 and H1299 cells. Furthermore, miR-25-3p mimic enhanced drug resistance, and accelerated cell invasion and metastasis. Moreover, miR-25-3p mimic resulted in the activation of PTEN/PI3K/AKT pathway. However, miR-25-3p inhibitors exhibited the opposite trend. We further identified PTEN as a potential target of miR-25-3p. PTEN knockout promoted cisplatin resistance, while PTEN mimic displayed opposite effects. Interestingly, miR-25-3p further boosted cisplatin resistance cells in vivo, and miR-25-3p inhibitors reduced the in-vivo tumor volume. MiR-25-3p/PTEN/PI3K/AKT axis might accelerate DDP tolerance in NSCLC, which may serve as a potential target for chemotherapy resistance in NSCLC., Graphical abstract more...
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- 2021
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37. Lnc NR2F1-AS1 Promotes Breast Cancer Metastasis by Targeting the MiR-25-3p/ZEB2 Axis.
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Zhai D, Zhou Y, Kuang X, Shao F, Zhen T, Lin Y, Wang Q, and Shao N
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- Humans, Female, Cell Line, Tumor, MCF-7 Cells, Cell Proliferation genetics, Cell Movement genetics, Gene Expression Regulation, Neoplastic genetics, COUP Transcription Factor I genetics, COUP Transcription Factor I metabolism, Zinc Finger E-box Binding Homeobox 2 genetics, Zinc Finger E-box Binding Homeobox 2 metabolism, Melanoma, Cutaneous Malignant, MicroRNAs genetics, MicroRNAs metabolism, Breast Neoplasms pathology, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, Neoplasms, Second Primary
- Abstract
Background: Long noncoding RNAs (lncRNAs) substantially affect tumor metastasis and are aberrantly expressed in various cancers. However, its role in breast cancer (BC) remains unclear. Methods: A microarray assay of differentially expressed lncRNAs in epithelial-mesenchymal transition (EMT) and non-EMT cells was performed. The prognostic value of lnc NR2F1-AS1 expression in patients with BC was analyzed using The Cancer Genome Atlas database. Lnc NR2F1-AS1 expression levels in different BC cell lines were assessed using quantitative real-time PCR. The role of lnc NR2F1-AS1 in BC cell metastasis was investigated in vitro and in vivo. Dual luciferase reporter assay and RNA immunoprecipitation were performed to investigate the relationship between lnc NR2F1-AS1, miR-25-3p, and ZEB2. Results: High levels of lnc NR2F1-AS1 were observed in BC cells undergoing EMT and were closely correlated with adverse prognosis in patients with BC. Lnc NR2F1-AS1 knockdown significantly inhibited BC cell migration, invasiveness in vitro, and metastasis in vivo. Mechanistically, lnc NR2F1-AS1 competitively binds to miR-25-3p to impede ZEB2 degradation, a positive EMT transcription factor in BC. Conclusions: Our study revealed a novel lnc NR2F1-AS1/miR-25-3p/ZEB2 axis in BC metastasis and that lnc NR2F1-AS1 may serve as a potential therapeutic target for BC metastasis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).) more...
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- 2023
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38. miR-25-3p reverses epithelial-mesenchymal transition via targeting Sema4C in cisplatin-resistance cervical cancer cells.
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Song, Jing and Li, Yue
- Abstract
Acquisition of epithelial-mesenchymal transition ( EMT) has recently been proposed as an important contributor of drug resistance in cervical cancer cells. However, the underlying mechanisms are still unclear. Micro RNAs play a crucial role in regulating EMT. The aim of this study was to explore the potential role of miR-25-3p in regulating EMT in cisplatin-resistant ( CR) cervical cancer cells. To this end, we established stable CR cervical cancer cells, HeLa- CR and CaSki- CR, and investigated the function of miR-25-3p in regulating EMT. It is found that CR cervical cancer cells possessed more EMT characteristics and demonstrated higher migratory abilities and invasiveness. miR-25-3p downregulation was also seen in HeLa- CR and CaSki- CR cells. Of note, ectopic expression of miR-25-3p reversed the EMT phenotype and sensitized CR cells to cisplatin via targeting Sema4C. Furthermore, stable overexpression of miR-25-3p in HeLa- CR cells suppressed tumor growth in mice, downregulated Sema4C and Snail, and upregulated E-cadherin compared with the control group. These results suggest that miR-25-3p is an important regulator of cervical cancer EMT and chemoresistance. Thus, upregulation of miR-25-3p could be a novel approach to treat cervical cancers that are resistant to chemotherapy. [ABSTRACT FROM AUTHOR] more...
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- 2017
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39. Plasma microRNAs are associated with acute exacerbation in idiopathic pulmonary fibrosis.
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Haiyan Min, Shanshan Fan, Shiyu Song, Yi Zhuang, Hui Li, Yongzheng Wu, Hourong Cai, Long Yi, Jinghong Dai, and Qian Gao
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- *
PULMONARY fibrosis , *DISEASE exacerbation , *BLOOD plasma , *PULMONARY fibrosis treatment , *MICRORNA , *GENE expression , *GENETICS - Abstract
Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has high short-term mortality with unknown causes. To predict this malignant condition in clinics is challenging. In this study, we aim to demonstrate whether there are miRNAs that differ between AE-IPF and stable IPF, which may be served as reliable biomarker for AE-IPF prediction. Methods: Human fibrotic-associated miRNAs arrays were designed to detect miRNAs expression in plasma of 3 AEIPF patients, 3 Stable-IPF (S-IPF) patients and 3 normal controls (NC). Differentially expressed miRNAs between AE-IPF and S-IPF patients were selected for further analyses. The validation studies were carried out in plasma of 12 AE-IPF patients, 45 S-IPF patients and 51 healthy control subjects. Signaling pathways and cellular processes interacted with validated miRNAs were predicted by DIANA-miRPath. Results: According to the array analysis, 6 miRNAs showed differentiated expression between AE-IPF and S-IPF patients (P < 0.05). In the validation studies, let-7d-5p was decreased in S-IPF and further decreased in AE-IPF, when compared to NC (0.0003 ± 0.0002 vs 0.003 ± 0.002, P < 0.01 and 0.0007 ± 0.0005 vs 0.003 ± 0.002, P < 0.01). While miR-25-3p was obviously decreased in S-IPF (0.0002 ± 0.0001 vs 0.0003 ± 0.0003, P < 0.01) but significantly increased in AE-IP (0.0023 ± 0.002 vs 0.0003 ± 0.0003, P < 0.01). In receiver-operator characteristic (ROC) curve analysis, the areas under the curve (AUCs) of miR-25-3p and let-7d-5p were 0.83 and 0.75, respectively. The sensitivity at fixed specificity of 90% was improved from 50% to 66.7% when the two miRNAs were combined. The functional prediction of miRNAs suggested that the loss of anti-fibrotic capacity and the gain of uncontrolled cell growth may be required in AE-IPF pathogenesis. Conclusions: In conclusion, miR-25-3p and let-7d-5p in plasma were differentially expressed between AE-IPF and S-IPF. A combination of these two miRNAs may be a potential biomarker for AE-IPF from IPF. [ABSTRACT FROM AUTHOR] more...
- Published
- 2016
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40. Exosomal transfer of miR‑25‑3p promotes the proliferation and temozolomide resistance of glioblastoma cells by targeting FBXW7
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Jianxin Wang, Bin Wang, and Tianxiao Li
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Male ,Cancer Research ,F-Box-WD Repeat-Containing Protein 7 ,Cell Survival ,Cell ,F-box and WD repeat domain-containing-7 ,temozolomide ,Biology ,Exosomes ,Exosome ,Flow cytometry ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,exosome ,Viability assay ,Cell Proliferation ,Oncogene ,medicine.diagnostic_test ,Brain Neoplasms ,glioblastoma ,Articles ,Cell cycle ,Xenograft Model Antitumor Assays ,Microvesicles ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,medicine.anatomical_structure ,miR-25-3p ,Oncology ,Drug Resistance, Neoplasm ,Gene Knockdown Techniques ,Cancer research ,Female - Abstract
Intrinsic or acquired resistance to temozolomide (TMZ) is a frequent occurrence in patients with glioblastoma (GBM). Accumulating evidence has indicated that the exosomal transfer of proteins and RNAs may confer TMZ resistance to recipient cells; however, the potential molecular mechanisms are not fully understood. Thus, the aim of the present study was to elucidate the possible role of exosomal microRNAs (miRNAs/miRs) in the acquired resistance to TMZ in GBM. A TMZ-resistant GBM cell line (A172R) was used, and exosomes derived from A172R cells were extracted. Exosomal miR-25-3p was identified as a miRNA associated with TMZ resistance. The potential functions of exosomal miR-25-3p were evaluated by reverse transcription-quantitative PCR, as well as cell viability, colony formation and soft agar assay, flow cytometry, western blot analysis, BrdU incorporation assay, tumor xenograft formation, luciferase reporter assay and RNA immunoprecipitation. It was found that A172R-derived exosomes promoted the proliferation and TMZ resistance of sensitive GBM cells. Moreover, miR-25-3p epxression was upregulated in the exosomes of A172R cells and in serum samples of patients with GBM treated with TMZ. The depletion of exosomal miR-25-3p partially abrogated the effects induced by the transfer of exosomes from A172R cells. By contrast, miR-25-3p overexpression facilitated the proliferation and TMZ resistance of sensitive GBM cells. F-box and WD repeat domain-containing-7 (FBXW7) was identified as a direct target of miR-25-3p. FBXW7 knockdown promoted the proliferation and TMZ resistance of GBM cells. Furthermore, the exosomal transfer of miR-25-3p promoted c-Myc and cyclin E expression by downregulating FBXW7. Our results provided a novel insight into exosomal microRNAs in acquired TMZ resistance of GBM cells. Besides, exosomal miR-25-3p might be a potential prognostic marker for GBM patients. more...
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- 2021
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41. MiR-25-3p targets PTEN to regulate the migration, invasion, and apoptosis of esophageal cancer cells via the PI3K/AKT pathway
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Zhuang Tong, Yanfeng Huang, Liang Zhang, Erdong Shen, Guolian Zhu, and Zhe Sun
- Subjects
0301 basic medicine ,PTEN ,Esophageal Neoplasms ,Biophysics ,migration ,Biochemistry ,Flow cytometry ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,esophageal cancer ,Viability assay ,Molecular Biology ,Protein kinase B ,Research Articles ,PI3K/AKT/mTOR pathway ,Cancer ,Cell Proliferation ,medicine.diagnostic_test ,biology ,Chemistry ,apoptosis ,PTEN Phosphohydrolase ,Cell Biology ,Transfection ,invasion ,Healthy Volunteers ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,miR-25-3p ,Apoptosis ,Case-Control Studies ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Background: Esophageal cancer (EC) is one of the most common malignant tumors of the digestive system. MiR-25-3p was proved to be a biomarker for the diagnosis and treatment of many cancers. MiR-25-3p was found to be high expressed in the blood of EC patients. The aim of the present study was to explore the effect of miR-25-3p and its target gene on EC. Methods: miR-25-3p expression in the blood of EC patients and EC cells was detected by RT-qPCR. The target of miR-25-3p was identified by bioinformatics and luciferase reporter assay. After transfection, cell viability, apoptosis, migration, and invasion were detected by MTT, flow cytometry, wound healing, and transwell assays, respectively. The expressions of PTEN, Bax, Bcl-2, cleaved Caspase-3, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blot. Results: MiR-25-3p was high expressed in the blood of EC patients and EC cells. MiR-25-3p targeted PTEN and inhibited the expression of PTEN. MiR-25-3p mimic increased the viability, migration, invasion and the expressions of Bcl-2, and inhibited the apoptosis and the expression of Bax and cleaved caspase-3 in EC cells. MiR-25-3p mimic also enhanced the expressions of p-PI3K and p-AKT and the ratios of p-PI3K/PI3K and p-AKT/AKT in EC cells. PTEN overexpression not only had an opposite effect of miR-25-3p mimic, but also reversed the effect of miR-25-3p mimic on EC cells. Conclusion: MiR-25-3p targeted PTEN to promote the migration and invasion, and inhibit apoptosis of EC cells via the PI3K/AKT pathway, which might provide a new therapeutic target for EC treatment. more...
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- 2020
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42. MicroRNA-148b-3p and MicroRNA-25-3p are overexpressed in fetuses with late-onset fetal growth restriction
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Morales-Roselló, José, García Gimenez, José Luis, Martinez Priego, Llucia, González-Rodríguez, Daymé, Mena-Mollá, Salvador, Maquieira Catalá, Angel, Loscalzo, Gabriela, Buongiorno, Silvia, Jakaite, Vaidile, Cañada Martínez, Antonio José, and Perales Marín, Alfredo more...
- Subjects
Late-onset fetal growth restriction ,miR-25-3p ,Micro-RNA ,miR-148b-3p ,MicroRNA ,Schwann cells ,Doppler ultrasound ,Schwann cell - Abstract
Objective: to describe a miRNA profile characteristic of late-onset growth restriction (FGR) and to investigate those pathways involved in their biochemical action. Material and methods: In a prospective study, 25 fetuses: 16 normal and 9 with FGR (estimated fetal weight, This is the pre-peer reviewed version of the following article: Morales-Roselló J, García-Giménez J, L, Martinez Priego L, González-Rodríguez D, Mena-Mollá S, Maquieira Catalá A, Loscalzo G, Buongiorno S, Jakaite V, Cañada Martínez A, J, Perales Marín A: MicroRNA-148b-3p and MicroRNA-25-3p Are Overexpressed in Fetuses with Late-Onset Fetal Growth Restriction. Fetal Diagn Ther 2020;47:665-674 (DOI: 10.1159/000507619). The copyright holder is the publisher. The final, published version is available at http://karger.com/?doi=10.1159/000507619 Funding sources: 1-iPlacenta project, European Union's Horizon 2020 Research and Innovation Programme, MarieSkłodowska-Curie grant agreement Number 765274, 2- VLC-Biomed Grant, Universidad de Valencia & Universidad Politécnica de Valencia, 3- Clinical Study Protocol X213220 Xoma, Hospital Universitario y Politécnico La Fe, 4- Charity Run "9 km 9 meses", Instituto de Investigación Sanitaria La Fe and Ayuntamiento de Torrente, Valencia, Spain. more...
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- 2020
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43. MicroRNA‑25‑3p regulates human nucleus pulposus cell proliferation and apoptosis in intervertebral disc degeneration by targeting Bim
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Zhifang Zhao, Youchen Ye, Jie Zheng, Kefeng Zhao, Ruozhang Wang, and Ran Wang
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Male ,Cancer Research ,Programmed cell death ,Nucleus Pulposus ,Cell ,Biochemistry ,Downregulation and upregulation ,microRNA ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Cell Proliferation ,intervertebral disc degeneration ,Bcl-2-Like Protein 11 ,Chemistry ,Cell growth ,apoptosis ,Articles ,Transfection ,Cell cycle ,Rats ,Cell biology ,Bcl-2 interacting mediator of cell death ,Disease Models, Animal ,MicroRNAs ,medicine.anatomical_structure ,miR-25-3p ,Gene Expression Regulation ,Oncology ,Apoptosis ,Molecular Medicine - Abstract
Intervertebral disc degeneration (IDD) is a degenerative disease of the spine originating from the intervertebral disc. MicroRNAs (miRNAs or miRs) are a group of endogenous small non‑coding RNAs that act on target genes and play a critical role in numerous biological processes. However, the underlying mechanism of miR‑25‑3p in IDD remains unclear. Therefore, the present study aimed to explore the role of miR‑25‑3p in the pathogenesis of IDD. The results demonstrated that miR‑25‑3p was downregulated in rat degenerative nucleus pulposus (NP) cells and that Bcl‑2 interacting mediator of cell death (Bim) was a direct target of miR‑25‑3p. Next, to investigate the effect of miR‑25‑3p on normal NP cell proliferation and apoptosis, NP cells were transfected with an miR‑25‑3p inhibitor, a negative control of miR‑25‑3p inhibitor, miR‑25‑3p inhibitor + control‑small interference RNA (siRNA) or miR‑25‑3p inhibitor + Bim‑siRNA for 48 h and cell proliferation and apoptosis were then analyzed. The results demonstrated that the miR‑25‑3p inhibitor could decrease NP cell proliferation and induce cell apoptosis, and these effects were reversed by Bim‑siRNA. In addition, an in vitro cell model of IDD was established by subjecting NP cells to 10 ng/ml interleukin (IL)‑1β for 24 h. Further experiments suggested that IL‑1β treatment induced a reduction in NP cell proliferation and an increase in cell apoptosis, which were prevented by the miR‑25‑3p mimic. All the effects of miR‑25‑3p mimic on IL‑1β‑treated NP cells were significantly reversed by Bim upregulation. These findings suggested that miR‑25‑3p may be a novel therapeutic target for IDD prevention. more...
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- 2020
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44. MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma
- Author
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Hua-Chun, Rao, Zhao-Ke, Wu, Si-da, Wei, Yun, Jiang, Qing-Xin, Guo, Jia-Wen, Wang, Chang-Xian, Chen, and Hui-Yong, Yang
- Subjects
Merlin ,miR-25-3p ,osteosarcoma ,proliferation ,apoptosis ,metastasis ,Original Research - Abstract
Purpose Moesin-ezrin-radixin-like protein (Merlin) has been identified as a tumor suppressor in several types of cancers. However, the biological function of Merlin in osteosarcoma remains unclear. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we sought to evaluate the regulation of Merlin expression by miR-25-3p and the role of the miR-25-3p/Merlin axis in osteosarcoma progression, with the aim of identifying a potential therapeutic target for osteosarcoma. Materials and Methods TCGA (The Cancer Genome Atlas) database was used to analyze the correlation between Merlin expression and prognosis. RT-qPCR and Western blotting analyses were performed to compare Merlin expression between normal and malignant cells. A dual-luciferase reporter assay was performed to evaluate the direct targeting of Merlin by miR-25-3p. We overexpressed miR-25-3p, or/and Merlin, in U-2 OS and 143B cells, and studied their cellular functions in vitro. MTT and colony formation assays were performed to determine the effects on cell growth. EdU and cell cycle assays were performed to analyze the effects in cell replication. We used annexin V-fluorescein isothiocyanate and propidium iodide to stain apoptotic cells, and analyzed the cells using flow cytometry. The effects on cell metastasis were studied in wound healing and transwell assays. Lastly, the underlying mechanism was determined in RT-qPCR and Western blotting experiments. Results Low Merlin expression was linked to poor prognosis. miR-25-3p was observed to directly target Merlin and downregulate its expression. miR-25-3p promoted cell growth, migration, and invasion, and inhibited apoptosis induced by cisplatin. Moreover, the overexpression of Merlin reversed the abovementioned effects of miR-25-3p. Further, the miR-25-3p/Merlin axis was observed to play an important role in the Hippo pathway, and regulated the expression of genes such as BIRC5, CTGF, and CYR61. Conclusion miR-25-3p functions as an oncogenic microRNA in osteosarcoma by targeting Merlin, and may serve as a potential therapeutic target for osteosarcoma. more...
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- 2020
45. A feature-based analysis identifies COL1A2 as a regulator in pancreatic cancer
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Lei Song, Jie Wu, Xiao-Qing Wei, XiangHuan Niu, ShuHong Tang, Jing Liu, and Qi Yu
- Subjects
musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,MiR-25-3p ,COL1A2 ,Regulator ,Computational biology ,Biology ,01 natural sciences ,Collagen Type I ,Cell Line, Tumor ,Pancreatic cancer ,Drug Discovery ,medicine ,Feature based ,Humans ,Cell Proliferation ,Pharmacology ,integumentary system ,010405 organic chemistry ,Gene Expression Profiling ,lcsh:RM1-950 ,General Medicine ,bioinformatics ,medicine.disease ,0104 chemical sciences ,Pancreatic Neoplasms ,010404 medicinal & biomolecular chemistry ,lcsh:Therapeutics. Pharmacology ,Function (biology) ,Research Paper - Abstract
This study aimed to identify genetic biomarkers in pancreatic cancer (PC) and explore its function in PC via a feature-base analysis of bioinformatics. OMIM and DisGeNET databases discovered 209 PC connected genes and then 516 connected genes were identified. We selected 29 genes according to optimal features and chose COL1A2, which had the highest expression, for the following experiment. The expression of COL1A2 was determined by qRT-PCR; cell proliferation was determined by MTT assay; migration and invasion after COL1A2 and miR-25-3p transfection was evaluated by Transwell assay. COL1A2 presented the highest expression in PC tissues, which was validated in functional experiments. MiR-25-3p suppressed the expression of COL1A2 in cell lines and inhibited migration, invasion and proliferation of PC cells. MiR-25-3p could suppress the expression of COL1A2 and inhibit the proliferation, migration and invasion of PC cells which provided a new idea for the detection and treatment of PC. more...
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- 2019
46. miR-25-3p promotes proliferation and inhibits autophagy of renal cells in polycystic kidney mice by regulating ATG14-Beclin 1
- Author
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Xiyue Wang, Xiaowen Kang, Liting Chen, Fanwu Kong, Guojian Liu, Ping Guo, Rui Yue, Yu Shang, and Ruomei Du
- Subjects
Male ,autophagy ,proliferation ,030232 urology & nephrology ,Vesicular Transport Proteins ,ATG14 ,Autophagy-Related Proteins ,Down-Regulation ,Mice, Transgenic ,macromolecular substances ,030204 cardiovascular system & hematology ,lcsh:RC870-923 ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Laboratory Study ,microRNA ,Polycystic kidney disease ,Medicine ,Animals ,Cell Proliferation ,Polycystic Kidney Diseases ,polycystic kidney disease ,business.industry ,Autophagy ,Epithelial Cells ,General Medicine ,lcsh:Diseases of the genitourinary system. Urology ,Polycystic kidney ,medicine.disease ,musculoskeletal system ,Up-Regulation ,MicroRNAs ,miR-25-3p ,Nephrology ,Cancer research ,cardiovascular system ,Beclin-1 ,business - Abstract
MicroRNAs are involved in the regulation of the autophagy and proliferation in several diseases. This study aims to verify the role of miR-25-3p in the proliferation and autophagy of renal cells in polycystic kidney disease (PKD). We found that kidney to body weight and blood urea content were increased in PKD mice. Cystic dilations were increased in kidney tissue from PKD mice, and autophagy-related protein ULK1 and the ratio of LC3-II/LC3-I were decreased, indicating autophagy was inhibited in PKD mice. In addition, miR-25-3p was upregulated in PKD mice, and inhibition of miR-25-3p decreased cystic dilations in kidney tissues, increased ULK1 expression and the ratio of LC3-II/LC3-I, indicating inhibition of miR-25-3p enhanced the autophagy in PKD. Besides, inhibition of miR-25-3p suppressed the proliferation of renal cells and downregulated E2F-1 and PCNA expressions. Importantly, miR-25-3p targetedly suppressed ATG14 expression in PKD cells. Finally, silencing ATG14 abolished the inhibition effect of miR-25-3p inhibitor on renal cell proliferation, and reversed the inhibition effect of miR-25-3p inhibitor on E2F-1 and PCNA expressions in in vitro and in vivo experiments, which suggested that ATG14 was involved in the regulation of miR-25-3p-mediated kidney cell proliferation. Therefore, inhibition of miR-25-3p promoted cell autophagy and suppressed cell proliferation in PKD mice through regulating ATG14. more...
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- 2020
47. miR-25-3p promotes endothelial cell angiogenesis in aging mice via TULA-2/SYK/VEGFR-2 downregulation
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Chong, Lian, Lei, Zhao, Jiacong, Qiu, Yang, Wang, Rencong, Chen, Zhen, Liu, Jin, Cui, Xiaonan, Zhu, Xuejun, Wen, Shenming, Wang, and Jinsong, Wang
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Male ,Aging ,Down-Regulation ,Endothelial Cells ,Vascular Endothelial Growth Factor Receptor-2 ,Gene Expression Regulation, Neoplastic ,Mice, Inbred C57BL ,MicroRNAs ,angiogenesis ,miR-25-3p ,endothelial cell ,Animals ,Syk Kinase ,Protein Tyrosine Phosphatases ,TULA-2 ,Cells, Cultured ,Signal Transduction ,Research Paper - Abstract
In aging, the regulation of angiogenesis is a dynamic and complex process. We aimed to identify and characterize microRNAs that regulate angiogenesis during aging. We showed that, in response to vascular endothelial senescence, microRNA-25-3p (miR-25-3p) plays the role of an angiogenic microRNA by targeting TULA-2 (T-cell ubiquitin ligand-2)/SYK (spleen tyrosine kinase)/VEGFR-2 (vascular endothelial growth factor receptor 2) signaling in vitro and in vivo. Mechanistic studies demonstrated that miR-25-3p inhibits a TULA-2/SYK/VEGFR-2 signaling pathway in endothelial cells. In old endothelial cells (OECs), upregulation of miR-25-3p inhibited the expression of TULA-2, which caused downregulation of the interaction between TULA-2 and SYK and increased phosphorylation of SYK Y323. The increased SYK Y323 phosphorylation level upregulated the phosphorylation of VEGFR-2 Y1175, which plays a vital role in angiogenesis, while miR-25-3p downregulation in YECs showed opposite effects. Finally, a salvage study showed that miR-25-3p upregulation promoted capillary regeneration and hindlimb blood flow recovery in aging mice with hindlimb ischemia. These findings suggest that miR-25-3p acts as an agonist of TULA-2/SYK/VEGFR-2 and mediates the endothelial cell angiogenesis response, which shows that the miR-25-3p/TULA-2 pathway may be potential therapeutic targets for angiogenesis during aging. more...
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- 2020
48. MiR-25-3p attenuates the proliferation of tongue squamous cell carcinoma cell line Tca8113.
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Xu, Jia-Ying, Yang, Li-Li, Ma, Chao, Huang, Yuan-Liang, Zhu, Gui-Xiang, and Chen, Qi-Lin
- Abstract
Abstract: Objective: To investigate the effects of miR-25-3p on the occurrence, development and proliferation of tongue squamous cell carcinoma cells. Methods: To establish tongue squamous cell carcinoma cell line Tca8113 that stably and highly express miR-25-3p using recombinant retroviral vector-mediated gene transfer method. The proliferation of transfected Tca8113 was detected by thiazolyl blue tetrazolium bromide (MTT) and cell colony formation assays. cyclinD1, p21
cip1 and p27kip1 mRNA expressions in the transfected Tca-8113 were detected by quantitative PCR. cyclinD1, p21, p27kip1 , AKT, p-AKT, FOXO1 and p-FOXO1 expressions in the transfected Tca8113 were detected by western blot analysis. In addition, miR-25-3p expression in the tongue squamous cell carcinoma cell line and tissue specimen was also detected by quantitative PCR. Results: Quantitative PCR showed that miR-25-3p expression in the tongue squamous cell carcinoma cell lines and tissue specimen was significantly lower than that in the adjacent tissue. MTT and cell colony formation assays showed that after miR-25-3p overexpression, the proliferation of transfected Tca8113 was obviously attenuated. Western blot analysis and quantitative PCR showed that after miR-25-3p overexpression, p21cip1 and p27kip1 expressions were upregulated, while cyclinD1, AKT, FOXO1 expressions were downregulated, and AKT and FOXO1 phosphorylation was inactivated in the transfected Tca8113 cells. Conclusions: MiR-25-3p inhibited the proliferation of tongue squamous cell carcinoma cells and regulated cell cycle-related protein expression, playing an important role in the occurrence and development of squamous cell carcinoma of the tongue. [Copyright &y& Elsevier] more...- Published
- 2013
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49. CircHSPG2 absence weakens hypoxia-induced dysfunction in cardiomyocytes by targeting the miR-25-3p/PAWR axis.
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Zhao Y, Wang S, Liu S, Yan Q, Li Y, and Liu Y
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Background: Circular RNAs (circRNAs) are important regulators in human cardiovascular diseases. Here, we investigated the role of circRNA heparan sulfate proteoglycan 2 (circHSPG2) in hypoxia-induced myocardial infarction (MI) and its associated mechanism., Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to examine RNA and protein expression. Cell viability was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Cell proliferation was assessed by 5-Ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay. Flow cytometry (FCM) analysis was carried out to analyze the apoptosis of AC-16 cells. Lactate dehydrogenase (LDH) assay was implemented to assess cell death. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the target relationship between microRNA-25-3p (miR-25-3p) and circHSPG2 or pro-apoptotic WT1 regulator (PAWR)., Results: Hypoxia treatment up-regulated the expression of circHSPG2 in AC-16 cells. Hypoxia exposure reduced the viability, suppressed the proliferation and induced the apoptosis of AC-16 cells, and these effects were diminished by the silence of circHSPG2. CircHSPG2 acted as a molecular sponge for miR-25-3p. CircHSPG2 absence-mediated effects on hypoxia-induced AC-16 cells were largely reversed by anti-miR-25-3p. miR-25-3p bound to the 3' untranslated region (3'UTR) of PAWR. PAWR overexpression largely counteracted miR-25-3p-mediated effects on hypoxia-induced AC-16 cells. CircHSPG2 positively regulated the expression of PAWR by acting as miR-25-3p sponge in AC-16 cells., Conclusions: CircHSPG2 silencing protected AC-16 cells against hypoxia-induced dysfunction by targeting miR-25-3p/PAWR axis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-22-197/coif). The authors have no conflicts of interest to declare., (2022 Cardiovascular Diagnosis and Therapy. All rights reserved.) more...
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- 2022
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50. Exosomes secreted by chronic hepatitis B patients with PNALT and liver inflammation grade ≥ A2 promoted the progression of liver cancer by transferring miR-25-3p to inhibit the co-expression of TCF21 and HHIP
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Deming Tan, Xiaoyu Fu, Lei Fu, Shifang Peng, Yujing Tang, Wanfeng Wu, and Yi Ouyang
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0301 basic medicine ,Male ,HHIP ,Apoptosis ,Exosomes ,Metastasis ,Mice ,0302 clinical medicine ,Basic Helix-Loop-Helix Transcription Factors ,Gene knockdown ,Membrane Glycoproteins ,medicine.diagnostic_test ,miR‐25‐3p ,Liver Neoplasms ,General Medicine ,Middle Aged ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Liver ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Original Article ,Liver cancer ,Adult ,Cell Survival ,Down-Regulation ,Mice, Nude ,Exosome ,Flow cytometry ,liver cancer ,03 medical and health sciences ,Young Adult ,Hepatitis B, Chronic ,medicine ,Animals ,Humans ,exosome ,Viability assay ,Cell Proliferation ,Inflammation ,TCF21 ,Cell growth ,business.industry ,Cell Biology ,Original Articles ,medicine.disease ,CHB ,MicroRNAs ,030104 developmental biology ,Cancer research ,business ,Carrier Proteins - Abstract
Objectives The current study aimed to investigate the mechanism by which exosomes secreted by CHB patients with PNALT and liver inflammation grade (≥A2) affected the development of liver cancer. Materials and methods Gene expression was assessed by RT‐PCR, Western blotting and immunohistochemistry. CCK‐8, colony formation, transwell, scratch‐wound and flow cytometry assays were used to detect cell viability, proliferation, apoptosis and metastasis. The interaction of TCF21 and HHIP was assessed by co‐immunoprecipitation assay. Luciferase reporter was used to detect the combination of TCF21/HHIP and miR‐25‐3p. Xenograft studies in nude mice manifested tumour growth ability of miR‐25‐3p. Bioinformatics analyses were conducted using TargetScan, EVmiRNA, TCGA, GEO, DAVID, COEXPEDIA, UALCAN, UCSC and the Human Protein Atlas databases. Results CHB‐PNALT‐Exo (≥A2) promoted the proliferation and metastasis of HepG2.2.15 cells. miR‐25‐3p was upregulated in CHB‐PNALT‐Exo (≥A2). miR‐25‐3p overexpression promoted cell proliferation and metastasis and was related to poor survival in patients with CHB‐PNALT (≥A2). The cell proliferation‐ and metastasis‐promoting functions of CHB‐PNALT‐Exo (≥A2) were abolished by miR‐25‐3p inhibitors. TCF21 directly interacted with HHIP. Inhibition of TCF21 or HHIP promoted cell proliferation and metastasis. Knockdown of TCF21 or HHIP counteracted the effects of CHB‐PNALT‐Exo (≥A2) containing miR‐25‐3p inhibitor on cell proliferation, metastasis and the expression of Ki67, E‐cadherin and caspase‐3/‐9. Conclusions Transfer of miR‐25‐3p by CHB‐PNALT‐Exo promoted the development of liver cancer by inhibiting the co‐expression of TCF21 and HHIP. more...
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- 2020
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