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Objective: To analyze the expression of pediatric Critical Case scoring (PCIS) combined with serum microRNA-125b and granulocyte colony stimulating factor (G-CSF) in children with viral encephalitis and its correlation with prognosis. Methods: 105 children with viral encephalitis admitted to our hospital from January 2022 to June 2023 were selected to be included in the observation group, and another 105 healthy physical examination children in the same period were selected to be included in the control group. All enrollees were subjected to PCIS scoring, and serum microRNA-125b and G-CSF expression levels were detected to analyze the variability of PCIS scoring, serum microRNA-125b, and G-CSF expression levels in children with viral encephalitis of different severity and the relationship with indicators of cerebral damage in the cerebrospinal fluid; with a follow-up of 6 months, the poor prognosis was recorded, and a multifactorial logistic regression and a multifactor logistic regression were used to measure the prognosis. Factor logistic regression and subject work characteristics (ROC) curves were used to analyze the relationship between PCIS score, serum microRNA-125b, G-CSF and poor prognosis. Results: The PCIS score of observation group was lower than that of control group, and the expression levels of serum microRNA-125b and G-CSF were higher than those of control group (P<0.05). Of the 105 children with viral encephalitis, 40 were severe and 65 were non-severe cases. The PCIS score of the critical group was lower than that of the non-critical group, and the expression levels of serum microRNA-125b and G-CSF were higher than those of the non-critical group (P<0.05). By Pearson correlation analysis, the children with viral encephalitis PCIS score, serum microRNA-125b, the expression level of G-CSF and myelin basic protein (MBP) in cerebrospinal fluid, brain type of creatine kinase (CK-BB), neuron specific enolization enzyme (NSE) expression levels were positively correlated (P<0.05). The multi-factor Logistic regression, PCIS score, serum microRNA-125b and G-CSF is children with viral encephalitis is an independent predictor of poor prognosis (P<0.05). The ROC curve analysis, PCIS score, serum microRNA-125b joint G-CSF prediction of prognosis of children with viral encephalitis, AUC is 0.923. Conclusion: PCIS score, serum microRNA-125b, and G-CSF are all associated with severity of illness in children with viral encephalitis, and the combination improves the level of prediction of poor prognosis. [ABSTRACT FROM AUTHOR]

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Background: Atherosclerosis (AS) is an inflammatory disease linked to vascular events, with dysregulation of microRNA (miR)-125b, contributing to cardiovascular disease pathogenesis. Moreover, there is evidence of the involvement of signal transducer and activator of transcription 3 (STAT3) and sirtuin 6 (SIRT6) in AS. This study aimed to survey the expression levels of miR-125b, STAT3, and SIRT6 in the peripheral blood mononuclear cells (PBMCs) of AS patients and controls, and to find their correlations with biochemical parameters and risk factors. Methods: This study included blood samples from 45 controls and 45 AS patients, with PBMCs isolated using Ficoll solution. Expression levels of miR-125b, STAT3, and SIRT6 were determined via quantitative Real Time-PCR. Results: The findings revealed a significant increase in miR-125b levels in patients compared to controls (P = 0.017). However, alterations in STAT3 and SIRT6 expression were not significant (P> 0.05). There was no substantial relationship between miR-125b and STAT3 (P = 0.522) or SIRT6 (P = 0.88). miR-125b showed a significant relationship with atherogenic indexes and creatinine (P<0.05), while the association of SIRT6 with HDL and creatinine was significant (P<0.05). STAT3 exhibited high diagnostic power for identifying individuals at risk of heart disease and hypertension (P<0.05). Conclusions: STAT3 can serve as a valuable biomarker for detecting AS and AS-related risk factors. miR-125b and SIRT6 may be associated with AS lipid metabolism. However, further studies with larger sample sizes are recommended to mechanistically elucidate the association of these genes. [ABSTRACT FROM AUTHOR]

Objective To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and β-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance. [ABSTRACT FROM AUTHOR]

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRwNP) has multiple clinical presentations, and predictors of successful treatment are correlated to different parameters. Differentially expressed microRNAs in nasal polyps emerge as possible facilitators of precise endotyping in this disease. We aimed to evaluate the correlation between the clinical parameters of CRSwNP and two different microRNAs. Materials and Methods: The expression of miR-125b and miR-203a-3p in nasal polyps (n = 86) and normal nasal mucosa (n = 20) was determined through microarray analysis. Preoperative workup included CT scan, nasal endoscopy, blood tests, symptoms and depression questionnaires. Results: MiR-125b showed significant overexpression in NP compared to the normal nasal mucosa. miR-125b expression levels were positively and significantly correlated with blood eosinophilia (p = 0.018) and nasal endoscopy score (p = 0.021). Although high CT scores were related to miR-125b overexpression, the correlation did not reach statistical significance. miR-203a-3p was underexpressed in nasal polyps and was significantly underexpressed in CRSwNP patients with environmental allergies. Conclusions: Both miR-125b and miR-203a-3p are potential biomarkers in CRSwNP. miR-125b also correlates with the clinical picture, while miR-203a-3p could help identify an associated allergy. [ABSTRACT FROM AUTHOR]

Introduction: MicroRNA-125b has been found to be down-regulated in many types of malignant tumours and diseases with excessive proliferation of keratinocytes, such as cutaneous squamous cell carcinoma and psoriasis. Cholesteatoma, which is mainly composed of keratinocytes, also has characteristics of abnormal proliferation similar to a malignant tumour. However, the expression and regulatory mechanisms of miR-125b and its downstream genes in cholesteatoma have not been clarified. Material and methods: Real time fluorescence quantitative PCR was applied to detect the expression of miR-125b in the cholesteatoma and corresponding retroauricular skin. Immunohistochemical staining and western blot were used to detect signal transducers and activators of transcription 3 (STAT3) and the downstream gene cyclin D1, survivin, and vascular endothelial growth factor (VEGF) in the cholesteatoma and corresponding retroauricular skin. The targeted regulatory relationship between miR-125b and STAT3 was confirmed by dual luciferase reporter assay. Proliferation and apoptosis of transfected HaCaT cells were detected by MTS, cell cycle, and apoptosis assays. Results: We observed down-regulation of miR-125b and up-regulation of STAT3, cyclin D1, survivin, and VEGF in cholesteatoma tissues. STAT3 was a direct target gene of miR-125b. Inhibition of miR-125b enhanced STAT3 and its downstream genes expression, promoted HaCaT cell proliferation, and inhibited apoptosis. Conclusions: The results of this study demonstrate that miR-125b can influence the growth of cholesteatoma by targeting STAT3 and its downstream genes, including cyclin D1, survivin, and VEGF, thus providing an opportunity to establish new medical therapy strategies and facilitating further study of the pathogenesis of cholesteatoma. [ABSTRACT FROM AUTHOR]

Bladder cancer is recognized as one of the top ten most common cancers worldwide. Activation of oncogenes, inactivation of tumor suppressor genes, and dysregulation of androgen signaling pathways are three major pathophysiological causes in the development of bladder tumors. Discovering potential biomarkers is required for the management and immunotherapy of bladder cancer. Melanoma-associated antigen (MAGE)-A6 and MAGE-A11 are two cancer-testis antigens that are potential coregulators of androgen receptors. MicroRNAs, especially miR-34a and miR-125b are two important tumor suppressors that play a critical role in regulating different signaling pathways and inhibiting tumor development. Twenty-nine surgical tissue biopsies were collected from patients with no preoperative chemotherapy or radiotherapy (26 males and, 3 females, mean age±SD: 62.4±13.3 years). Seventeen adjacent uninvolved tissues with no abnormalities upon histological examination were considered normal controls (14 males and, 3 females, mean age±SD: 64.2±7.4 years) . Quantitative PCR was performed to evaluate the gene expression level of MAGE-A6, MAGE-A11, miR-34a, and miR-125b in bladder cancer biopsies. MAGE-A6 and MAGE-A11 expressions were significantly increased in bladder tumors compared with normal tissues. However, the expression levels of miR-34a and miR-125b were significantly downregulated in bladder tumor tissues. Interestingly, the expression level of all these genes was significantly associated with tumor grade, pathological stage (pT), and muscular invasion. MAGE-A6 and MAGE-A11 can be considered potential markers for the diagnosis and immunotherapy of bladder tumors. Furthermore, the modulation of miR-34a and miR-125b gene expression in association with increased MAGE-A6 and MAGE-A11 genes could open a new horizon in the improvement of bladder cancer. [ABSTRACT FROM AUTHOR]

A hypoxic microenvironment is a common feature of skin wounds. Our previous study demonstrated that three-dimensional coculture of umbilical cord-derived mesenchymal stem cells (ucMSCs) and endothelial cells facilitates cell communication and host integration in skin tissue engineering. Here, we aimed to identify the mechanism by which ucMSCs affect endothelial cells under hypoxic conditions after skin injury. We demonstrate that hypoxia enhances the exosome-mediated paracrine function of ucMSCs, which increases endothelial cell proliferation and migration. In a mouse full-thickness skin injury model, ucMSC-derived exosomes can be taken up by endothelial cells and accelerate wound healing. Hypoxic exosomes lead to a better outcome than normoxic exosomes by promoting proliferation and inhibiting apoptosis. Mechanistically, microRNA-125b (miR-125b) transcription is induced by hypoxia in ucMSCs. After being packaged into hypoxic exosomes and transported to endothelial cells, miR-125b targets and suppresses the expression of tumor protein p53 inducible nuclear protein 1 (TP53INP1) and alleviates hypoxia-induced cell apoptosis. Inhibition of miR-125b-TP53INP1 interaction attenuates the protective effect of hypoxic exosomes. Moreover, artificial agomiR-125b can accelerate wound healing in vivo. Our findings reveal communication between ucMSCs and endothelial cells via exosomal miR-125b/TP53INP1 signaling in the hypoxic microenvironment and present hypoxic exosomes as a promising therapeutic strategy to enhance cutaneous repair.

Nasal polyps (NPs) are multifactorial soft growths inside the nasal passages and are associated with chronic inflammation that originate from the nasal and paranasal sinus mucosae. This study focused on the role of microRNA (miR)-125b and the molecules associated with NP development. Differentially expressed miRNAs between nasal tissues from patients with chronic rhinosinusitis (CRS) with NP (CRSwNP) and CRS without NP (CRSsNP) were screened using microarray analysis. A murine model of CRSwNP was established. The expression of miR-125b in murine tissues was examined using reverse transcription quantitative polymerase chain reaction. Candidate upstream regulators of miR-125b were predicted using bioinformatics tools, and the binding relationship between specificity protein 1 (Sp1) and miR-125b was validated using luciferase and chromatin immunoprecipitation assays. Altered expression of Sp1 and miR-125b was induced to evaluate their relevance to the progression of NPs. miR-125b expression was significantly upregulated in NP tissues from patients with CRSwNP. Sp1 was confirmed as an upstream regulator that promotes miR-125b transcription in NPs. Overexpression of Sp1 reduced levels of d-dimer (an indicator of fibrinogen degradation products) and tissue-type plasminogen activator (t-PA) but increased eosinophil cationic protein and peroxidase levels, as well as the levels of inflammatory factors interleukin-5 (IL-5) and IL-8 in murine NP tissues. However, these trends were reversed after miR-125b downregulation. Sp1 and miR-125b were found to activate the Wnt/β-catenin signaling pathway in NPs. This study demonstrated that Sp1, an upstream transcription factor of miR-125b, accumulates on the miR-125b promoter to activate its transcription, which induces inflammation and fibrin deposition in NP by activating the Wnt/β-catenin axis. [ABSTRACT FROM AUTHOR]

Background Breast cancer is a common type of tumor in women worldwide. MicroRNAs have been identified as regulators in many human cancers. The aim of this study was therefore to investigate the functional role of miR‐125b in regulating breast cancer progression. Methods We used the StarBase database to investigate the expression of miRNA‐125b in breast cancer and adjacent normal tissues. MMP11 3′‐UTR construct and luciferase reporter assays was performed for target genes. Cell proliferation was evaluated by CCK‐8 and colony formation assay. The migration and invasion were assessed by transwell assay. Results Luciferase reporter assays showed miRNA‐125b directly targeted MMP11. miRNA‐125b by transfection with its mimic in breast cancer cells significantly suppressed breast cancer cell proliferation and migration. Western blot revealed that overexpression of miRNA‐125b substantially reduced MMP11 protein expression. We used the UALCAN database to investigate the expression of MMP11 in human breast cancer and adjacent normal tissues. In addition, we found that miRNA‐125b spoiled MMP11 induced breast cancer cell proliferation and migration promotion effect. Conclusions miRNA‐125b mimic inhibited proliferation, migration, and invasion of breast cancer cells through targeting MMP11 protein.

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRwNP) has multiple clinical presentations, and predictors of successful treatment are correlated to different parameters. Differentially expressed microRNAs in nasal polyps emerge as possible facilitators of precise endotyping in this disease. We aimed to evaluate the correlation between the clinical parameters of CRSwNP and two different microRNAs. Materials and Methods: The expression of miR-125b and miR-203a-3p in nasal polyps (n = 86) and normal nasal mucosa (n = 20) was determined through microarray analysis. Preoperative workup included CT scan, nasal endoscopy, blood tests, symptoms and depression questionnaires. Results: MiR-125b showed significant overexpression in NP compared to the normal nasal mucosa. miR-125b expression levels were positively and significantly correlated with blood eosinophilia (p = 0.018) and nasal endoscopy score (p = 0.021). Although high CT scores were related to miR-125b overexpression, the correlation did not reach statistical significance. miR-203a-3p was underexpressed in nasal polyps and was significantly underexpressed in CRSwNP patients with environmental allergies. Conclusions: Both miR-125b and miR-203a-3p are potential biomarkers in CRSwNP. miR-125b also correlates with the clinical picture, while miR-203a-3p could help identify an associated allergy.

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background MicroRNA-125b (miR-125b) is downregulated in human cutaneous squamous cell carcinoma (CSCC). However, its function in CSCC has yet to be extensively explored. Here, we analyze the relationship between signal transducer and activator of transcription 3 (STAT3) and miR-125b in CSCC. Methods Western blotting and quantitative RT-PCR were used to determine the expression of the miR-125b–STAT3 axis in human CSCC tissues and cell lines. The direct regulatory effect of miR-125b on STAT3 expression was assessed using a luciferase reporter gene assay and RNA immunoprecipitation assay. The MTT assay and flow cytometry were used to determine the role of the miR-125b–STAT3 axis in CSCC cell proliferation and apoptosis. Results MiR-125b expression levels were significantly lower in CSCC cell lines and tissues than in normal cell lines and tissues. STAT3 was identified as the direct target of miR-125b. Upregulation of miR-125b and downregulation of STAT3 suppressed cell proliferation and promoted cell apoptosis. Cyclin D1 and Bcl2 were identified as the downstream targets of the miR-125–STAT3 axis. Conclusions Our findings indicate that miR-125b acts as a tumor suppressor in CSCC by targeting the STAT3 pathway. This observation increases our understanding of the molecular mechanisms of CSCC. Therapies aimed at activating miR-125b or inhibiting STAT3 signaling should be explored as potential treatments for CSCC.

The purpose of this study is to investigate the role of microRNA-125b (miR-125b) and its mechanism in spinal cord injury (SCI) by targeting Smurf1. After loss-and gain-function approaches were conducted in SCI rat models and neural stem cells (NSCs) isolated from foetal rats, the Basso-Beattie-Bresnahan (BBB) score was calculated, and related protein expression was determined by Western blot analysis and cell apoptosis by TUNEL staining. NSC viability was detected by CCK-8, migration abilities by Transwell assay and apoptosis by flow cytometry. The relationship between miR-125b, Smurf1 and KLF2 was evaluated by dual-luciferase reporter gene experiments, Co-IP and in vivo ubiquitin modification assays. Inhibition of miR-125b and KLF2 and the up-regulation of Smurf1 and ATF2 were observed in SCI rats. BBB scores were elevated, the expression of Nestin, NeuN, GFAP, NF-200 and Bcl-2 protein was enhanced but that of Bax protein was reduced, and cell apoptosis was inhibited in SCI rats after up-regulating miR-125b or silencing ATF2. Smurf1 was a target gene of miR-125b, which promoted KLF2 degradation through its E3 ubiquitin ligase function, and KLF2 repressed the expression of ATF2 in NSCs. The results in vivo were replicated in vitro. miR-125b overexpression promotes neurological function recovery after SCI. [ABSTRACT FROM AUTHOR]

Background: Laryngocarcinoma is the most frequent head and neck malignant tumor. MALAT1 have a role in promoting cell proliferation and metastasis in several tumors. This research aimed to investigate the great roles of MALAT1in laryngocarcinoma. Methods: Overall, 54 cases of laryngocarcinoma tissues pathological specimens and paracancerous tissues were collected by surgical resection from the Department of Otolaryngology-Head and Neck Surgery at the Shandong Provincial Hospital affiliated to Shandong University, China from Jan 2012 to Oct 2015. The microRNA and protein levels of genes were evaluated by RT-qPCR and western blot. The proliferative and invasive ability were calculated usingCCK8 and transwell assays. Kaplan-Meier method was used to assess the survival of laryngocarcinoma patients. Results: In laryngocarcinoma tissues and cells, lncRNA MALAT1 expression was significantly increased compared to normal tissues and cells. LncRNA MALAT1 promotes proliferation and migration of laryngocarcinoma cells. LncRNA MALAT1 upregulates HMGA1 expression by acting as a competitive endogenous RNA (ceRNA) for miR-125b. Rescue experiments showed that microRNA-125b inhibitor reversed the change in cell viability and invasion induced by sh-MALAT1. Down regulation of lncRNA MALAT1 inhibits laryngocarcinoma proliferation and invasion by modulating miR-125b /HMGA1. Conclusion: LncRNA MALAT1 promotes the development of laryngocarcinoma by regulating the expression level of HMGA1 by acting as a miR-125b ceRNA and may be considered as a new strategy for the development of laryngocarcinoma.

This study aimed to explore the molecular regulatory network among microRNA-125b (miR-125b), forkhead box Q1 (FOXQ1), prostaglandin-endoperoxide synthase 2 (PTGS2), and cyclin-dependent kinase 5 (CDK5), as well as their effects on cell apoptosis, neurite outgrowth, and inflammation in Alzheimer disease (AD). Rat embryo cerebral cortex neurons and nerve growth factor–stimulated PC12 cells were insulted by Aβ1−42 to construct two AD cellular models. Negative control (NC) inhibitor, miR-125b inhibitor, NC siRNA, FOXQ1 siRNA, PTGS2 siRNA, and CDK5 siRNA were transferred into the two AD cellular models alone or combined. Then, cell apoptosis, neurite outgrowth, proinflammatory cytokines, miR-125b, FOXQ1, PTGS2, and CDK5 expressions were detected. MiR-125b inhibition facilitated neurite outgrowth but suppressed cell apoptosis and proinflammatory cytokines (tumor necrosis factor-α, interleukin 1β, and interleukin 6); meanwhile, it upregulated FOXQ1 but downregulated PTGS2 and CDK5. Furthermore, FOXQ1 inhibition promoted cell apoptosis and proinflammatory cytokines but repressed neurite outgrowth; PTGS2 inhibition achieved the opposite effects; CDK5 inhibition attenuated cell apoptosis, whereas it less affected neurite outgrowth and inflammation. Notably, FOXQ1 inhibition attenuated, whereas PTGS2 inhibition elevated the effect of miR-125b inhibition on regulating neurite outgrowth, cell apoptosis, and proinflammatory cytokines. As for CDK5 inhibition, it enhanced the effect of miR-125b inhibition on regulating cell apoptosis, but less impacted the neurite outgrowth and proinflammatory cytokines. Additionally, PTGS2 inhibition and CDK5 inhibition both reversed the effect of FOXQ1 inhibition on regulating cell apoptosis, neurite outgrowth, and proinflammatory cytokines. In conclusion, targeting miR-125b alleviates AD progression via blocking PTGS2 and CDK5 in a FOXQ1-dependent way.

This study aimed to explore the molecular regulatory network among microRNA-125b (miR-125b), forkhead box Q1 (FOXQ1), prostaglandin-endoperoxide synthase 2 (PTGS2), and cyclin-dependent kinase 5 (CDK5), as well as their effects on cell apoptosis, neurite outgrowth, and inflammation in Alzheimer disease (AD). Rat embryo cerebral cortex neurons and nerve growth factor–stimulated PC12 cells were insulted by Aβ1−42 to construct two AD cellular models. Negative control (NC) inhibitor, miR-125b inhibitor, NC siRNA, FOXQ1 siRNA, PTGS2 siRNA, and CDK5 siRNA were transferred into the two AD cellular models alone or combined. Then, cell apoptosis, neurite outgrowth, proinflammatory cytokines, miR-125b, FOXQ1, PTGS2, and CDK5 expressions were detected. MiR-125b inhibition facilitated neurite outgrowth but suppressed cell apoptosis and proinflammatory cytokines (tumor necrosis factor-α, interleukin 1β, and interleukin 6); meanwhile, it upregulated FOXQ1 but downregulated PTGS2 and CDK5. Furthermore, FOXQ1 inhibition promoted cell apoptosis and proinflammatory cytokines but repressed neurite outgrowth; PTGS2 inhibition achieved the opposite effects; CDK5 inhibition attenuated cell apoptosis, whereas it less affected neurite outgrowth and inflammation. Notably, FOXQ1 inhibition attenuated, whereas PTGS2 inhibition elevated the effect of miR-125b inhibition on regulating neurite outgrowth, cell apoptosis, and proinflammatory cytokines. As for CDK5 inhibition, it enhanced the effect of miR-125b inhibition on regulating cell apoptosis, but less impacted the neurite outgrowth and proinflammatory cytokines. Additionally, PTGS2 inhibition and CDK5 inhibition both reversed the effect of FOXQ1 inhibition on regulating cell apoptosis, neurite outgrowth, and proinflammatory cytokines. In conclusion, targeting miR-125b alleviates AD progression via blocking PTGS2 and CDK5 in a FOXQ1-dependent way. [ABSTRACT FROM AUTHOR]

Copyright of China Tropical Medicine is the property of China Tropical Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Previous studies have shown that microRNA (miR)-125b plays important roles in several human cancer types. The aim of the present study was to analyze the potential roles of miR-125b in papillary thyroid carcinoma (PTC). It was found that miR-125b was downregulated in PTC and its expression was affected by clinical stages. Glucose transporter 1 (GLUT1) was upregulated in PTC and was negatively correlated with miR-125b. In PTC cells, overexpression of miR-125b suppressed glucose uptake and downregulated GLUT1. Furthermore, GLUT1 overexpression reduced the effects of miR-125b overexpression on glucose uptake. Moreover, miR-125b overexpression suppressed PTC cell proliferation. GLUT1 overexpression promoted the proliferation of PTC cells and reduced the effects of miR-125b overexpression on cancer cell proliferation. Overall, miR-125b decreased glucose uptake in PTC cells by downregulating GLUT1. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Breast cancer is a common type of tumor in women worldwide. MicroRNAs have been identified as regulators in many human cancers. The aim of this study was therefore to investigate the functional role of miR‐125b in regulating breast cancer progression. Methods: We used the StarBase database to investigate the expression of miRNA‐125b in breast cancer and adjacent normal tissues. MMP11 3′‐UTR construct and luciferase reporter assays was performed for target genes. Cell proliferation was evaluated by CCK‐8 and colony formation assay. The migration and invasion were assessed by transwell assay. Results: Luciferase reporter assays showed miRNA‐125b directly targeted MMP11. miRNA‐125b by transfection with its mimic in breast cancer cells significantly suppressed breast cancer cell proliferation and migration. Western blot revealed that overexpression of miRNA‐125b substantially reduced MMP11 protein expression. We used the UALCAN database to investigate the expression of MMP11 in human breast cancer and adjacent normal tissues. In addition, we found that miRNA‐125b spoiled MMP11 induced breast cancer cell proliferation and migration promotion effect. Conclusions: miRNA‐125b mimic inhibited proliferation, migration, and invasion of breast cancer cells through targeting MMP11 protein. [ABSTRACT FROM AUTHOR]

Background/Aims: Chondrocyte apoptosis is largely responsible for cartilage degeneration in osteoarthritis (OA). MicroRNAs (miRNAs) play an important role in chondrogenesis and cartilage remodeling. This study explored the effect of miR-125b on inflammatory injury in chondrogenic cells. Methods: LPS was used to simulate inflammatory injury in murine chondrogenic ATDC5 cell lines. Targeting effect of miR-125b on MIP-1α 3’UTR was assessed by dual luciferase activity assay. Regulatory effect of miR-125b on MIP-1α expression and the potential regulatory mechanism on inflammatory injury were assessed by Western blot. Results: miR-125b expression was decreased in LPS-induced ATDC5 cells and overexpression of miR-125b inhibited LPS-induced cell viability decline, the rise of apoptosis and inflammatory factors’ productions. MIP-1α expression was negatively related to miR-125b, and miR-125b directly targeted with 3’UTR of MIP-1α. Knockdown of miR-125b promoted LPS-induced inflammatory response via upregulation of MIP-1α. miR-125b expression in LPS-induced ATDC5 cells was negatively related with activations of NF-κB and JNK signaling pathways. Overexpression of miR-125b inhibited LPS-induced inflammation injury via suppressing MIP-1α expression and inhibiting activations of NF-κB and JNK signaling pathways. Conclusion: miR-125b could play an important role in inflammatory injury of chondrogenic cells and miR-125b affected inflammatory injury of ATDC5 cells via regulating expression of MIP-1α and regulating NF-κB and JNK signaling pathways.

Introduction: Exosomes derived from Adipose-Derived Stem Cells (ADSCs-Exo) have been implicated in the enhancement of wound repair in Diabetic Foot Ulcers (DFU)., Objective: The current research was designed to explore the therapeutic potential and underlying mechanisms of ADSCs-Exo modified with microRNA-125b (miR-125b) in the context of DFU., Methods: Rat models with DFU and human umbilical vein endothelial cells (HUVECs) subjected to high glucose (HG) conditions served as experimental systems and were administered miR-125b-engineered ADSCs-Exo. Then, the expressions of CD34, Ki-67, angiogenesis-related factors (VEGF and TGFβ-1), angiogenesis inhibitor DLL-4, and inflammation-related proteins (TLR-4 and IL-6) were detected., Results: MiR-125b was upregulated in ADSCs-Exo. MiR-125b-mimics transfection in ADSCs- Exo reduced inflammatory infiltration and promoted granulation formation and wound healing in wound tissues. MiR-125b-mimics-modified ADSCs-Exo injection increased the expression of CD34, Ki-67, VEGF, and TGFβ-1, whereas decreased the expression of DLL-4, TLR-4, and IL-6 in wound tissues of DFU rats. In addition, miR-125b-mimics-ADSCs-Exo injection reversed the negative effects of HG on the proliferation, migration, and angiogenesis of HUVECs, as well as the positive effects of cell apoptosis. Moreover, miR-125b-inhibitor-ADSCs-Exo injection had the opposite effects to miR-125b-mimics-ADSCs-Exo., Conclusion: ADSCs-Exo promoted wound healing of DFU rats, especially when overexpressing miR-125b., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: MicroRNA-125b (miR-125b) is downregulated in human cutaneous squamous cell carcinoma (CSCC). However, its function in CSCC has yet to be extensively explored. Here, we analyze the relationship between signal transducer and activator of transcription 3 (STAT3) and miR-125b in CSCC. Methods: Western blotting and quantitative RT-PCR were used to determine the expression of the miR-125b–STAT3 axis in human CSCC tissues and cell lines. The direct regulatory effect of miR-125b on STAT3 expression was assessed using a luciferase reporter gene assay and RNA immunoprecipitation assay. The MTT assay and flow cytometry were used to determine the role of the miR-125b–STAT3 axis in CSCC cell proliferation and apoptosis. Results: MiR-125b expression levels were significantly lower in CSCC cell lines and tissues than in normal cell lines and tissues. STAT3 was identified as the direct target of miR-125b. Upregulation of miR-125b and downregulation of STAT3 suppressed cell proliferation and promoted cell apoptosis. Cyclin D1 and Bcl2 were identified as the downstream targets of the miR-125–STAT3 axis. Conclusions: Our findings indicate that miR-125b acts as a tumor suppressor in CSCC by targeting the STAT3 pathway. This observation increases our understanding of the molecular mechanisms of CSCC. Therapies aimed at activating miR-125b or inhibiting STAT3 signaling should be explored as potential treatments for CSCC. [ABSTRACT FROM AUTHOR]

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Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood driven by aberrant pathways of T-cell activation. T helper 17 (Th17)/regulatory T cell (Treg) imbalance plays critical roles in the pathogenesis of arthritis. MicroRNA-125b (miR-125b) was upregulated after the activation of the initial CD4+ T cells, and could regulate the differentiation of CD4+ T cells. However, the effects of miR-125b on Th17/Treg imbalance and differentiation of Th17/Treg cells remain unknown. Methods: In this study, we evaluated the expression of miR-125b in the peripheral blood mononuclear cells (PBMCs) of children with JIA, and the relationship of miR-125b with Th17/Treg imbalance. Then, we used lentivirus vector-mediated overexpression technology to investigate the regulatory function of miR-125b in CD4+ T cells or dendritic cell/CD4+ T co-culture system. Results: Decreased miR-125b expression in PBMCs and CD4+ T cells of JIA patients was negatively correlated with the ratio of Th17/Treg cells. It also correlated negatively with retinoic acid receptor-related orphan receptor γt but positively with Forkhead box protein 3 at transcriptional levels. Furthermore, we found that miR-125b overexpression inhibited Th17 cell differentiation, whereas facilitated the differentiation of Treg cells. MiR-125b upregulation led to the decrease of Th17-secreting cytokines but the increase of the Treg-secreting cytokines. Conclusions: Our results demonstrate that miR-125b participated in regulating Th17/Treg cell differentiation and imbalance in JIA patients. These findings provide novel insight into the critical role of miR-125b in the Th17/Treg imbalance of JIA, and raise the distinct possibility that miR-125b may prove to be a potential therapeutic target for JIA. [ABSTRACT FROM AUTHOR]

Gallbladder carcinoma (GBC) is the most common malignant tumor of the biliary tract. The incidence rate of gallbladder cancer ranks sixth among gastrointestinal types of cancer, and its incidence is increasing each year. Further clarification of the pathogenesis of GBC is essential, and identification of novel effective treatments is required. It has been previously demonstrated that high expression of the anti-apoptotic protein cellular Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein (c-FLIP) in GBC inhibited apoptosis in gallbladder cancer cells. In subsequent experiments, it was observed that microRNA (miR)-125b could target c-FLIP and inhibit the protein expression of c-FLIP by binding to the 3′untranslated regions of c-FLIP mRNA. In addition, the expression of miR-125b in GBC was significantly decreased, and the growth of gallbladder cancer cells was inhibited by the overexpression of miR-125b. The present study demonstrated that miR-125b could suppress the proliferation of gallbladder cancer cells by targeting c-FLIP. c-FLIP enriched the target gene pathway of miR-125b and may serve as a novel target for the treatment of GBC. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are aberrantly expressed in a variety of cancer types. The lncRNA IGF1R antisense imprinted non-protein coding RNA (IRAIN) is associated with various cancer types, yet the role of IRAIN in multiple myeloma (MM) progression remains unclear. In the present study it was identified that IRAIN may act as a tumor suppressor in MM, whilst microRNA (miR)-125b may promote tumorigenesis. Downregulation of IRAIN significantly increased the expression of miR-125b. Furthermore, by using dual-luciferase reporter assays, IRAIN was identified as a target of miR-125b. Knockdown of IRAIN promoted MM cell proliferation in vitro. Thus, expression levels of IRAIN may be used to predict the clinical prognosis of patients with MM and may be a novel therapeutic target for treating MM. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to determine the relationships between microRNA-20a and microRNA-125b expression and apoptosis and inflammation in a rat model of spinal cord injury (SCI) using microscopy, immunohistochemistry, and molecular biology. Methods: Sixty-one rats were divided into three groups: a control group that was not subjected to any operation; a sham-operated group; and an experimental group that was subjected to spinal cord compression. The experimental group was further subdivided into two subgroups: the experimental control group, which did not receive any drug treatment; and the methylprednisolone treatment group, which received 30 mg/kg methylprednisolone on day 0 followed by 10 mg/kg/day methylprednisolone from days 1–14. Results: Tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 levels increased in the experimental control group on days 1 and 3, and decreased in the experimental control group and methylprednisolone treatment group on days 7 and 14. Caspase-3 levels increased in the experimental control group on day 1, and decreased in the experimental control group and methylprednisolone treatment group on days 3, 7, and 14. MicroRNA-20a expression was upregulated in the experimental control group on days 1 and 3, and microRNA-125b expression was downregulated on days 3 and 7. Conclusions: After SCI, upregulated microRNA-20a expression and increased proinflammatory cytokines may lead to an increase in inflammation. MicroRNA-125b may be associated with caspase-3, and microRNA-125b downregulation may inhibit apoptosis. Although the results of this study suggest potential relationships between microRNA-20a and microRNA-125b expression and apoptosis and inflammation in SCI, further studies are needed to confirm microRNA-20a and microRNA-125b as biomarkers in SCI and to develop new strategies for the treatment of SCI. [ABSTRACT FROM AUTHOR]

Liquid biomarkers for the early detection of resistance to chemotherapy are important for improving prognosis. This study investigated the usefulness of plasma exosomal microRNA-125b (ex-miRNA-125b) for the early detection of resistance to modified fluorouracil, leucovorin and oxaliplatin (mFOLFOX6)-based first-line chemotherapy in patients with advanced or recurrent (advanced/recurrent) colorectal cancer (CRC). First, ex-miRNAs associated with resistance to mFOLFOX6-based chemotherapy were profiled via miRNA microarray analysis. In this analysis, ex-miR-125b exhibited the greatest upregulation in patients with progressive disease (PD) compared with the findings for patients with stable disease (SD) and healthy controls. Next, another 55 patients with advanced/recurrent CRC who received mFOLFOX6-based first-line chemotherapy underwent a validation study of ex-miR-125b. Blood samples were collected before and during treatment until tumor progression. Ex-miRNA levels were measured via TaqMan microRNA assays. Patients with CRC had significantly higher ex-miR-125b levels than healthy controls. In patients with partial responses, ex-miR-125b levels at the Response Evaluation Criteria in Solid Tumors (RECIST) judgment point were significantly lower than those measured before treatment. In patients with SD, ex-miR-125b levels did not differ before and during treatment. In patients with PD, ex-miR-125b levels at the RECIST judgment point were significantly higher than those measured before treatment. These changes in ex-miR-125b levels were significantly different between groups even 1 month after the initiation of chemotherapy. Progression-free survival (PFS) was significantly worse in patients with high baseline ex-miR-125b levels than in those with low levels. In the Cox analysis, baseline ex-miR-125b levels and KRAS mutation were indicated to be independent prognostic factors for PFS. The present results suggest that plasma ex-miR-125b levels may be useful for the early detection of resistance to mFOLFOX6-based first-line chemotherapy. Furthermore, ex-miR-125b before chemotherapy is a predictive biomarker for PFS in patients with advanced/recurrent CRC. [ABSTRACT FROM AUTHOR]

Melanoma is an invasive and malignant type of tumor with unsatisfactory therapeutic outcomes. The present study aimed to detect the expression levels of microRNA (miR)-125b in formalin-fixed paraffin-embedded (FFPE) melanoma tissues and the association of its expression levels with the clinical features, diagnosis and prognosis of melanoma. Expression levels of miR-125b in 29 FFPE melanoma specimens (16 primary and 13 metastatic tumors), and 16 intradermal nevus (IDN) specimens as a control, were detected by reverse transcription-quantitative PCR. Associations among miR-125b expression and mortality, patient age and sex, tumor location and size, lymph node metastasis (LNM) and TNM stage were analyzed by t-test. The diagnostic value of miR-125b for melanoma was evaluated by receiver operating characteristic (ROC) curve analysis. Prognosis of patients in the microRNA-125b low- and high-expression groups was analyzed by Fisher's exact test. The association between miR-125b expression and the overall survival of patients with melanoma was assessed using Kaplan-Meier curve analysis and a Cox proportional hazards model. The results revealed that the expression levels of miR-125b in primary and metastatic melanomas were significantly lower than those in the IDN control group (P<0.05), and the expression levels of miR-125b in the metastatic group were significantly lower than those in the primary group (P<0.05). In addition, the expression levels of miR-125b were significantly associated with LNM (P=0.001) and TNM stage (P=0.004), but not with age, sex, tumor size or location (P>0.05). ROC curve analysis revealed that the area under the curve (AUC) was 0.880, with a 95% CI of 0.777–0.984 (P<0.05). The overall survival rate of the patients with a low expression level of miR-125b (20.0%) was lower than that of patients with a high expression level of miR-125b (64.3%) (P<0.05). miR-125b expression was an independent predictor of overall survival in patients with melanoma [hazard ratio (HR), 0.252; 95% CI, 0.087–0.729]. Overall, these findings indicated that a low expression level of miR-125b was associated with higher LNM and TNM stage in patients with melanoma, and that this has a certain diagnostic value. miR-125b may be used for the early screening of melanoma and determining the prognosis of patients with melanoma, and may be a potential target for the treatment of the disease. [ABSTRACT FROM AUTHOR]

Background/Aims: MicroRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to chemotherapy resistance. However, its role in epithelial ovarian carcinoma remains unknown. The goal of this study was to identify the relationship between miR-125b and the epithelial-mesenchymal transition (EMT) in ovarian cancer. Methods: In total, 55patients with epithelial ovarian cancer (EOC) were included in our study. The relative expression of miR-125b was measured using real-time polymerase chain reaction (RT-PCR).The protein expression of SET and EMT-related indicators in cell lines were assessed by Western blot. The regulation of SET by miR-125b was confirmed using luciferase reporter assays. The effect of miR-125b on metastasis was evaluated using an in vivo metastasis model. Results: miR-125b expression was markedly lower in the EOC specimens. Ectopic expression of miR-125b in EOC cells significantly inhibited tumor invasion.miR-125b expression was negatively associated with both EMT and SET expression, in vivo and in vitro. Mechanistic studies identified SET as a direct target of miR-125b, and the downregulation of SET, observed during tumor migration, was affected by the overexpression of miR125b. Conclusion: miR-125b suppresses EOC cell migration and invasion by targeting the SET protein, and this study may provide a novel mechanism for understanding the progression of EOC.

Background MicroRNA‐125b (miR‐125b) has been shown to regulate vascular calcification (VC), and serum miR‐125b levels are a potential biomarker for estimating the risk of uremic VC status. However, it is unknown whether clinical features, including chronic kidney disease–mineral bone disorder molecules, affect serum miR‐125b levels. Methods and Results Patients receiving chronic dialysis for ≥3 months were recruited from different institutes. Serum miR‐125b and chronic kidney disease–mineral bone disorder effectors, including intact parathyroid hormone, 25‐OH‐D, fibroblast growth factor‐23, osteoprotegerin, and fetuin‐A, were quantified. We used multivariate regression analyses to identify factors associated with low serum miR‐125b levels and an area under receiver operating characteristic curve curve to derive optimal cutoffs for factors exhibiting close associations. Further regression analyses evaluated the influence of miR‐125b on VC risk. Among 223 patients receiving chronic dialysis (mean age, 67.3 years; mean years of dialysis, 5.2), 54 (24.2%) had high serum miR‐125b levels. Osteoprotegerin (P=0.013), fibroblast growth factor‐23 (P=0.006), and fetuin‐A (P=0.036) were linearly associated with serum miR‐125b levels. High osteoprotegerin levels independently correlated with high serum miR‐125 levels. Adding serum miR‐125b levels and serum osteoprotegerin levels (≥400 pg/mL) into models estimating the risk of uremic VC increased the area under receiver operating characteristic curve values (for models without miR‐125b/osteoprotegerin, with miR‐125b, and both: 0.74, 0.79, and 0.81, respectively). Conclusions Serum osteoprotegerin levels ≥400 pg/mL and serum miR‐125b levels synergistically increased the accuracy of estimating VC risk among patients receiving chronic dialysis. Taking miR‐125b and osteoprotegerin levels into consideration when estimating VC risk may be recommended.

Abstract Background Osteoarthritis is an age-related disorder of bone-joint that causes pain and disability in middle and older people. This study aimed to investigate the potential effects of long non-coding RNA (lncRNA) THRIL on lipopolysaccharide (LPS)-induced osteoarthritis cell injury model (ATDC5 cell inflammatory injury), as well as the possible internal molecular mechanisms. Methods Cell viability and apoptosis were assessed using CCK-8 assay and Guava Nexin assay, respectively. Cell transfection was conducted to change the expression of THRIL and microRNA-125b (miR-125b) in ATDC5 cells. qRT-PCR was performed to detect the expression of THRIL, miR-125b and pro-inflammatory cytokines IL-6, TNF-α and monocyte chemotactic protein 1 (MCP-1) in ATDC5 cells. ELISA was used to measure the concentrations of IL-6, TNF-α and MCP-1 in culture supernatant of ATDC5 cells. Finally, the protein expression of key factors involved in cell apoptosis, inflammatory response, JAK1/STAT3 and NF-κB pathways were evaluated using western blotting. Results LPS significantly induced ATDC5 cell inflammatory injury and up-regulated the expression of THRIL. Overexpression of THRIL aggravated the LPS-induced ATDC5 cell inflammatory injury. Suppression of THRIL had opposite effects. Moreover, THRIL negatively regulated the expression of miR-125b in ATDC5 cells. miR-125b participated in the effects of THRIL overexpression on LPS-induced ATDC5 cell inflammatory injury. Furthermore, overexpression of THRIL enhanced the LPS-induced JAK1/STAT3 and NF-κB pathways activation by down-regulating miR-125b. Conclusion THRIL exerted pro-inflammatory roles in LPS-induced osteoarthritis cell injury model. Overexpression of THRIL promoted LPS-induced ATDC5 cell inflammatory injury by down-regulating miR-125b and then activating JAK1/STAT3 and NF-κB pathways. Highlights • LPS induced ATDC5 cell inflammatory injury; • LPS up-regulated the expression of THRIL in ATDC5 cells; • THRIL was involved in the LPS-induced ATDC5 cell inflammatory injury; • miR-125b participated in the effects of THRIL on LPS-induced ATDC5 cell injury; • THRIL aggravated LPS-induced JAK1/STAT3 and NF-κB pathways activation in ATDC5 cells. [ABSTRACT FROM AUTHOR]

Abstract Cardiac fibrosis is an important cardiac remodeling event in the development of inflammation dilated cardiomyopathy （iDCM）. We have previously observed that degradation enhancer of androgen receptor (ASC-J9®) could improve cardiac inflammation and fibrosis. Using Primary CFs, we demonstrated that ASC-J9® attenuates the expression of miR-125b, which subsequently inhibits the generation of collagen. In contrast, overexpressed AR in CFs induced collagen production, increases mir-125b.We also found that inhibition of miR-125b attenuates fibrosis which induced by the overexpression of AR. Our results indentify the functional role for AR as a regulator of cardiac fibrosis due to myocarditis and further show that AR exerts its effect by increasing microRNA-125b expression. Treatment with degradation enhancer of AR limits cardiac fibrosis in iDCM, thereby providing potentially a therapeutic approach for patients with iDCM. Highlights • ASC-J9, a enhancer of AR degradation, attenuation of heart fibrosis in EAM. • Androgen receptor regulates cardiac fibrosis in EAE by increasing microRNA-125b expression. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of inhibiting the expression of miR-125b on the migration and invasion of the triple negative breast cancer (TNBC) cells and to explore its mechanism. Methods MDA-MB-468 cells were divided into four groups; the miR-125b inhibitor group, negative control group (NC group), blank control group, and TNF-α group. The miR-125b inhibitors (miR-125b inhibitor group) and unrelated sequences (NC group) were transfected into MDA-MB-468 cells, respectively. At 48 h after transfection, 10 ng/mL TNF-α was added to the miR-125b inhibitor group, NC group, and TNF-α group for 72 h, while the blank control group was given only PBS solution. Scratch test and Transwell assay was used to observe the migration and invasion abilities. Fluorescent quantitative PCR was used to detect the expression of miR-125b. Western blotting was used to detect phosphorylated nuclear factor-KB (NFkB) p65 protein and epithelial-mesenchymal transition (EMT)-related proteins E-cadherin and Vimentin. Results The migration rate and the number of penetrating cells were in the following order: TNF-α group > blank control group > miR-125b inhibitor group (all P < 0.05). The expression of phosphorylated NF-kB p65 and Vimentin decreased by miR-125b inhibition; NC group and TNF-α group > blank control group > miR-125b inhibitor group (both P < 0. 05) , while the expression of E-cadherin was increased; NC group and TNF-α group < blank control group < miR-125b inhibitor group (P < 0. 05) , and no significant differences were found in the indexes between the NC group and TNF-α (all P>0.05). Conclusion Inhibiting miR-125b expression may inhibit TNF-α-indueed cell migration and invasion by interfering with NF-kB activity and inhibiting EMT in cells. [ABSTRACT FROM AUTHOR]

Objective To detect the expression of miR-125b in the nasal polyps and to explore its possible mechanism. Methods Thirty cases of nasal polyps and 16 cases of normal inferior turbinate were collected, and the expression of miR-125b was detected by real-time quantitative PCR. We transfected miR-125b mimics to epithelial cells of nasal polyps. CCK-8 assay and flow cytometry was used to detect the effects of the expression of miR-125b on proliferation and apoptosis of epithelial cells of nasal polyps. Western blotting was used to detect the expression of PI3K/Akt signaling pathway-related proteins. Results The expression of miR-125b in the nasal polyps was lower than that in the normal inferior turbinate (P < 0.05); the overexpression of miR-125b in the epithelial cells of nasal polyps inhibited the cell proliferation and increased the apoptosis (both P < 0.05). At the same time, the expression of PI3KCD and p-Akt protein decreased (both P <0.05). Conclusion The expression of miR-125b inthe nasal polyps decreases, and miR-125b may promote the proliferation and inhibit apoptosis of epithelial cells of nasal polyps by negatively regulating the activity of PI3K/Akt signaling pathway, and thereby induce the formation and development of nasal polyps. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the predictive value of baseline serum microRNA (miRNA)-125b for nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). A total of 66 patients with Be antigen (HBeAg)-positive CHB received NAs therapy for 144 weeks. Serum miRNA-125b levels were measured at the baseline, while hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg) and alanine aminotransferase (ALT) levels were measured throughout treatment. Stepwise logistic regression analysis was performed to identify predictors of treatment response. The results indicated that baseline serum miR-125b (OR=4.377; P=0.006), HBsAg (OR=0.120; P=0.010), ALT >5× upper limit of normal (ULN; OR=11.726; P=0.018) and undetectable HBV DNA at week 24 (OR=7.828; P=0.021) were independent predictors of complete response (CR) at 144 weeks (CR is defined as HBV DNA <500 IU/ml and HBeAg seroconversion). The baseline serum miRNA-125b combined with baseline HBsAg level yielded an area under the receiver-operating curve of 0.852 in discriminating CR and non-CR at 144 week. The combination of baseline miRNA-125b ≥1.7 and ALT >5× ULN had a positive predictive value 80% for CR at 144 weeks. The combination of baseline miRNA-125b ≥1.7 and HbsAg ≤4.4 (log10 IU/ml) had a negative predictive value of CR at 144 weeks of 100%. Together, these results suggest that baseline miRNA-125b is a reliable predictor of HBeAg seroconversion following NAs treatment. The present study may be used as a basis for the use of baseline miRNA-125b to optimize treatment prior to NAs therapy. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the expression of microRNA (miR)‑125b in patients with Alzheimer's disease (AD) and to determine its potential role in AD. Mouse neuroblastoma Neuro2a APPSwe/Δ9 cells were used to generate an in vitro AD model. The results demonstrated that the expression levels of miR‑125b were markedly increased in patients with AD compared with in the normal group. In addition, overexpression of miR‑125b significantly inhibited cell proliferation, induced apoptosis, and enhanced inflammation and oxidative stress in an in vitro model of AD model. Furthermore, overexpression of miR‑125b significantly promoted amyloid precursor protein and β‑secretase 1 expression and β‑amyloid peptide production, and suppressed sphingosine kinase 1 (SphK1) protein expression in vitro. These findings suggested that miR‑125b may regulate AD, and neuronal cell growth and apoptosis, via the regulation of inflammatory factors and oxidative stress by SphK1; therefore, miR‑125b may be involved in the development of AD. [ABSTRACT FROM AUTHOR]

Background/Aims: Chondrocyte apoptosis is largely responsible for cartilage degeneration in osteoarthritis (OA). MicroRNAs (miRNAs) play an important role in chondrogenesis and cartilage remodeling. This study explored the effect of miR-125b on inflammatory injury in chondrogenic cells. Methods: LPS was used to simulate inflammatory injury in murine chondrogenic ATDC5 cell lines. Targeting effect of miR-125b on MIP-1α 3’UTR was assessed by dual luciferase activity assay. Regulatory effect of miR-125b on MIP-1α expression and the potential regulatory mechanism on inflammatory injury were assessed by Western blot. Results: miR-125b expression was decreased in LPS-induced ATDC5 cells and overexpression of miR-125b inhibited LPS-induced cell viability decline, the rise of apoptosis and inflammatory factors’ productions. MIP-1α expression was negatively related to miR-125b, and miR-125b directly targeted with 3’UTR of MIP-1α. Knockdown of miR-125b promoted LPS-induced inflammatory response via upregulation of MIP-1α. miR-125b expression in LPS-induced ATDC5 cells was negatively related with activations of NF-κB and JNK signaling pathways. Overexpression of miR-125b inhibited LPS-induced inflammation injury via suppressing MIP-1α expression and inhibiting activations of NF-κB and JNK signaling pathways. Conclusion: miR-125b could play an important role in inflammatory injury of chondrogenic cells and miR-125b affected inflammatory injury of ATDC5 cells via regulating expression of MIP-1α and regulating NF-κB and JNK signaling pathways. [ABSTRACT FROM AUTHOR]

Aim: Early hepatocellular carcinoma (HCC) recurrence after curative resection is a known poor prognostic factor. We aimed to identify microRNAs associated with recurrence after curative HCC resection. Methods: To identify risk factors for early recurrence and metastasis, 694 patients who underwent primary curative HCC resection were analyzed. We evaluated microRNA expression in cancerous and non‐cancerous tissues by microarray and quantitative PCR analyses using 16 HCC samples. We defined patients who had a recurrence within 1 year of resection as the early recurrence (ER) group, patients who had a recurrence within 1–5 years as the late recurrence (LR) group, and patients who did not recur during the 5‐year observation period as the no recurrence (NR) group. We examined the relationship between microRNA expression and clinical features. Results: Multivariate analysis revealed that α‐fetoprotein >31 ng/mL, tumor size >4 cm, and intrahepatic metastasis (IM) were significant factors. Afterwards, microarray analyses revealed that microRNA (miR)‐125b‐5p and miR‐148a‐3p were significantly downregulated in recurrent cases. The ratio of miR‐125b‐5p expression in cancerous versus non‐cancerous tissue (miR‐125b ratio), but not miR‐148a‐3p, was significantly lower in the ER group. Early recurrence was associated with reduced overall survival compared with the LR and NR group. The miR‐125b ratio was significantly lower in the ER group than in the LR and NR groups. Multivariate analysis showed that a low miR‐125b ratio and IM were independently associated with ER and disease‐free survival. Conclusions: Assessing tissue miR‐125b‐5p expression and IM is useful for stratifying patients at risk of early HCC recurrence after curative resection. [ABSTRACT FROM AUTHOR]

MircroRNAs (miRNAs) are considered as essential regulators in the tumorigenesis and chemoresistance of multiple cancer types. In the present study, it was demonstrated that the expression levels of miR-125b were significantly downregulated in the tissues of patients with breast cancer (BC), as well as the BC cell lines in vitro. To study the association between chemoresistance and miR-125b in BC, doxorubicin (DOX)-resistant MCF-7 (MCF-7/R) cells were established, and gain- and loss-of-function experiments were performed. It was demonstrated that the overexpression of miR-125b increased the sensitivity of MCF-7/R cells to DOX. Furthermore, it was revealed that the sensitization of miR-125b mimics to DOX-induced cell death was regulated by the hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) vector and HAX-1 small interfering RNA. These results emphasized the notable function of miR-125b and its target of HAX-1 in regulating DOX-resistance. In addition, it was demonstrated that the miR-125b mimics promoted the loss of the mitochondrial membrane potential and the generation of reactive oxygen species induced by DOX treatment in MCF-7/R cells. These data suggest that the miR-125b-HAX-1-mitochondria pathway has a notable function in the treatment of DOX-resistant BC cells, which may provide a novel target for the chemotherapy of BC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Spinal cord injury (SCI) is a severe trauma to the central nervous system. Long non-coding RNAs have been reported to play essential roles in spinal cord injury. This study mainly explored the role of micro- 125 in the regulation of spinal cord injury by regulating STAT3. MATERIALS AND METHODS: The stable mouse model of cervical spinal cord contusion was established by Infinite Horizon spinal cord striker, and the model mice' motor function was analyzed. Bioinformatics databases were used to screen the target mRNAs of micro-125b. qRTPCR was performed to detect the expression of micro-125b and its target genes in injury area of mice' spinal cord. Western Blot and ELISA were introduced to detect the expression of inflammation and apoptosis-related proteins in each group. The recovery status of spinal cord after SCI was assessed by motor function scores and axon counts of mice in each group. RESULTS: Micro-125b appeared to be significantly down-regulated over-time after SCI. JAK1 and STAT1, two important neuregulin proteins, were predicted to be the target genes of micro- 125b, and overexpression of micro-125b induced the decrease of phosphorylated JAK1 and STAT1. Enhanced micro-125b expression also allowed axons from the injury area of spinal cord to extend into the outer periphery of the damaged area, thus improving the motor function of the injured rats. Besides, overexpression of micro-125b demonstrated significant neuronal protective effects by reducing apoptosis and inflammatory responses in neurons. CONCLUSIONS: Our data revealed that micro- 125b was down-regulated in injured spinal cord, and overexpression of micro-125b promoted the repair and regeneration following spinal cord injury through the regulation of the JAK/ STAT pathway. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is considered as one of the most common neural degenerative diseases in human. Although the continuous investigations about AD have been made in recent decades, the pathogenesis of this disease is still not definitely confirmed. MicroRNA-125b ( miR-125b ) is extensive expressed in many types of human tissues and played pivotal regulatory roles in diverse biological process. In the present study, we aimed to explore the roles of miR-125b in regulating neurons cell apoptosis under AD condition. The possible molecular mechanisms were also investigated. We found that miR-125b was up-regulated in patients with AD. Transfection with miR-125b significantly enhanced the apoptosis of neurons cells and phosphorylation of Tau by activation of cyclin-dependent kinase 5 (CDK5) and p35/25. Forkhead box Q1 ( FOXQ1 ) was the direct target gene of miR-125b , which involved in the effects of miR-125b on neurons cell apoptosis and phosphorylation of Tau. Our research interpreted the mechanism of up-regulation of miR-125b in pathological Tau phosphorylation and AD occurrence. miR-125b may be a novel regulator of AD progress and could be as a therapeutic target for AD therapy. [ABSTRACT FROM AUTHOR]

microRNA-125b (miR-125b) has been reported to be increased in rheumatoid arthritis (RA). However, the role of miR-125b in RA remains to be fully elucidated. We aimed to explore the functional role of miR-125b in RA, as well as the underlying mechanism. The expression of miR-125b in serum and synovial tissues of patients with RA and healthy controls was confirmed. In addition, the levels of miR-125b in lipopolysaccharide (LPS)-stimulated fibroblast-like synoviocytes (FLS) were also measured. FLS were transfected with miR-125b mimic, antisense oligonucleotides (ASO)-miR-125b, pcDNA-inhibitor of NF-κB (IκB)-α or corresponding controls, and then stimulated with LPS or incubated with nuclear factor kappa B (NF-κB) inhibitors pyrrolidine dithiocarbamate (PDTC). The effects of miR-125b abnormal expression on pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β and NF-κB pathway key factors phospho-p65 (p-p65) and IκB-α were assessed. Pearson correlation analysis was performed to assess the relationship between miR-125b expression and pro-inflammatory cytokines expression. Result showed that, the levels of miR-125b were significantly increased in RA serum and synovial tissues, as well as in LPS-stimulated FLS (P < 0.01). miR-125b overexpression statistically increased the expression of TNF-α, IL-6, IL-1β and p-p65 (P < 0.05 or P < 0.01), but markedly decreased IκB-α (P < 0.05). Contrary results were obtained by miR-125b downregulation. Additionally, there were strong positive relationships between miR-125b and TNF-α (R 2 = 0.7569, P < 0.000), IL-6 (R 2 = 0.8479, P < 0.000), and IL-1β (R 2 = 0.8037, P < 0.000). Moreover, the upregulated levels of pro-inflammatory cytokines were markedly decreased by PDTC (P < 0.01) and further downregulated by co-transfection with pcDNA-IκB-α (P < 0.01). In conclusion, our results suggest that elevated miR-125b promotes inflammation in RA by activation of NF-κB pathway. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the effect of peripheral blood miR-125b expression on severity and prognosis in children with viral encephalitis (VE). Children with VE (severe and mild groups) were grouped into VE group, and 40 healthy children as control group. Plasma RNA was extracted, and real-time quantitative PCR was conducted to detect miR-125b relative expression. Associations of miR-125b expression with clinical characteristics and prognosis of VE children were analyzed. Area under ROC curve (AUC) was calculated to evaluate the accuracy of the prognostic value of miR-125b. Univariate analysis and logistic regression analysis were performed to analyze risk factors of the prognoses of VE children. The plasma miR-125b expression was higher in the VE group than in the control group and higher in the severe group than the mild group. MiR-125b expression was associated with status convulsion, hemiplegia, multiple organ injuries, and stress hyperglycemia in VE children. Patients with poor prognosis exhibited higher miR-125b expression than those with good prognosis, and the rate of high miR-125b expression of the patients with poor prognosis (64.10%, 25/39) was higher than that in those with good prognosis (28.92%, 24/83). The AUC of miR-125b expression to predict prognosis of VE children was 0.833. When the cutoff value was 1.715, the diagnostic sensitivity (87.2%), specificity (71.1%), and accuracy (76.2%) were the highest. Status convulsion, stress hyperglycemia, and miR-125b were considered as risk factors for poor prognosis in VE children. Peripheral blood miR-125b expression may be correlated with the severity and prognosis of VE in children. [ABSTRACT FROM AUTHOR]

MicroRNA-125b (miR-125b) has been reported to be upregulated in several kinds of leukemia, suggesting that miR-125b plays a role in Leukemia development. In this study, it was shown that miR-125b expression level decreased in response to 1α, 25-dihydroxy-vitamin D3 (1,25D 3 ) in a dose- and time-dependent manner and miR-125b blocked 1,25D 3 -induced monocytic differentiation of U937 cells. In addition, miR-125b decreased mRNA expression of myelomonocytic differentiation markers, including CD11c, CD18 and CD64 and arrested the cell cycle at the S phase in U937 and HL60 cells. Fes was identified as a novel direct target of miR-125b and miR-125b could also reduce the expression levels of PU.1 and macrophage colony-stimulating factor receptor (MCSFR). Furthermore, Fes was found to be involved in monocytic differentiation via upregulation of PU.1 and MCSFR and Fes siRNA could also inhibit 1,25D 3 -induced monocytic differentiation of U937 and HL60 cells and decrease mRNA expression of CD11c, CD18 and CD64. Importantly, the inhibition of Fes siRNA on 1,25D 3 -induced monocytic differentiation could be rescued by transfection with miR-125b inhibitor. Our data highlights an important role of miR-125b in AML progression, implying the potential application of miR-125b in AML therapy. [ABSTRACT FROM AUTHOR]