Search

Breast cancer (BRCA) is one of the major threats to women's health worldwide. This study focuses on the roles of sorbin and SH3 domain‐containing protein 2 (SORBS2) protein and microRNA‐138‐5p in the progression of BRCA, analyzing their regulatory effects on cancer cell proliferation, cell cycle, and migration ability. Using bioinformatics tools and experimental methods, the study found that SORBS2 is commonly underexpressed in BRCA. Additionally, it demonstrated that microRNA‐138‐5p can significantly inhibit tumor growth by suppressing SORBS2 expression, providing new molecular targets for BRCA treatment. [ABSTRACT FROM AUTHOR]

To investigate the effect and its mechanism of oleuropein on the oxidative damage and apoptosis of astrocytes induced by oxygen-glucose deprivation, and its effect on circ_TTC3 and microRNA-138-5p. Astrocytes were divided into control group, oxygen-glucose deprivation group, oxygen-glucose deprivation+oleuropein 25 μmol/l, 50 μmol/l, 100 μmol/l groups, oxygen-glucose deprivation+si-negative control, si-circ_TTC3 group, oxygen-glucose deprivation+oleuropein+plasmid cloning deoxyribonucleic acid plasmid cloning deoxyribonucleic acid and plasmid cloning deoxyribonucleic acid-circ_TTC3 group. In comparison with the control group, the inhibiting rate of cell growth, apoptosis rate, malondialdehyde, lactate dehydrogenase levels and circ_TTC3 expression of astrocytes in the oxygen-glucose deprivation group were increased, while superoxide dismutase activity and miR-138-5p expression were declined (p<0.05). Compared to the oxygen-glucose deprivation group, the proliferative inhibiting rate, apoptosis rate, malondialdehyde, lactate dehydrogenase levels and circ_TTC3 expression of astrocytes in the oxygen-glucose deprivation+oleuropein 25 μmol/l group, oxygen-glucose deprivation+oleuropein 50 μmol/l group, and oxygen-glucose deprivation+oleuropein 100 μmol/l group were all weakened, superoxide dismutase activity and microRNA-138-5p expression were enhanced (p<0.05), and all were concentration-dependent. After silencing circ_TTC3, circ_TTC3 expression, malondialdehyde, lactate dehydrogenase levels, cell proliferation inhibition rate and apoptosis rate in astrocytes in the oxygen-glucose deprivation+si-circ_TTC3 group were all lower than those in oxygen-glucose deprivation+si-negative control group, while the superoxide dismutase activity was higher than that in oxygen-glucose deprivation+si-negative control group (p<0.05). Circ_TTC3 targeted and regulated microRNA- 138-5p. Circ_TTC3 level, malondialdehyde and lactate dehydrogenase levels, cell proliferation inhibition rate, and apoptosis rate in astrocytes in the oxygen-glucose deprivation+oleuropein+ plasmid cloning deoxyribonucleic acid-circ_TTC3 group were all higher than those in oxygen-glucose deprivation+oleuropein+plasmid cloning deoxyribonucleic acid group, and there was a decrease of superoxide dismutase activity in the oxygen-glucose deprivation +oleuropein+plasmid cloning deoxyribonucleic acid-circ_TTC3 group compared with oxygen-glucose deprivation+oleuropein+plasmid cloning deoxyribonucleic acid group (p<0.05). Oleuropein could reduce oxidative stress and apoptosis, thereby protecting astrocytes from damage induced by oxygen-glucose deprivation by upregulating circ_TTC3 to target microRNA-138-5p. [ABSTRACT FROM AUTHOR]

Both circular RNA eukaryotic translation initiation factor 6 (circEIF6) and microRNA (miR)-138-5p participate in thyroid cancer (TC) progression. Nevertheless, the relationship between them remains under-explored. Hence, this research ascertained the mechanism of circEIF6 in TC via miR-138-5p. After TC tissues and cells were harvested, circEIF6, miR-138-5p, and lipase H (LIPH) levels were assessed. The binding relationships among circEIF6, miR-138-5p, and LIPH were analyzed. The impacts of circEIF6, miR-138-5p, and LIPH on the invasive and proliferative abilities of TPC-1 cells were examined by Transwell and EdU assays. Tumor xenograft in nude mice was established for in vivo validation of the impact of circEIF6. CircEIF6 expression was high in TC cells and tissues. Additionally, miR-138-5p was poor and LIPH level was high in TC tissues. Mechanistically, circEIF6 competitively bound to miR-138-5p to elevate LIPH via a competitive endogenous RNA mechanism. Silencing of circEIF6 reduced TPC-1 cell proliferative and invasive properties, which was annulled by further inhibiting miR-138-5p or overexpressing LIPH. Likewise, circEIF6 silencing repressed the growth of transplanted tumors, augmented miR-138-5p expression, and diminished LIPH expression in nude mice. Conclusively, circEIF6 silencing reduced LIPH level by competitive binding to miR-138-5p, thus subduing the proliferation and invasion of TPC-1 cells. [ABSTRACT FROM AUTHOR]

Xiaojin Feng,1,2 Jialing Hu,1 Fenfang Zhan,1 Deqiang Luo,3 Fuzhou Hua,1,2 Guohai Xu1,2 1Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang, Jiangxi 330006, People’s Republic of China; 3Department of Intensive Care Unit, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Guohai Xu; Fuzhou HuaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaTel +86-791-86299131Email xuguohai1@sina.com; 415134607@qq.comPurpose: Neuroinflammation is an essential causative factor in the pathogenesis and progression of cognitive impairment. The present study aims to evaluate the critical role of microRNA-138-5p (miR-138-5p) in hippocampal neuroinflammation and cognitive impairment through the NLRP3/caspase-1 signaling pathway in rats.Material and Methods: We established the cognitive impairment rat model and RM (Rat microglia) microglial cellular inflammation model by intracerebroventricular (icv) injection or stimulation of lipopolysaccharide (LPS). Morris water maze (MWM) and Y-maze tests were performed to assess the cognitive behaviors. Quantitative real-time polymerase chain reaction (qRT-PCR), Enzyme-linked immune-sorbent assay (ELISA) and Western blot analysis were utilized to evaluate mRNA or protein expression. Bioinformatic analysis and dual-luciferase reporter gene assay were performed to verify the targeting relationship between NLRP3 and miR-138-5p. Besides, Hematoxylin and eosin (H&E) staining and immunohistochemistry were applied to observe the neuronal morphology and detect the positive cells of the hippocampus, respectively.Results: Compared to the control groups, LPS-treated rats exhibited significantly impaired learning and memory in MWM and Y-maze tests. The expression of NLRP3, caspase-1 and pro-inflammation cytokines (IL-1β and IL-18) were upregulated, while miR-138-5p was downregulated both in rat hippocampus and RM cells treated with LPS. MiR-138-5p is downregulated in microarray data of cognitive impairment animals and could directly target the 3ʹ-UTR of NLRP3. Furthermore, upregulation of miR-138-5p improved impaired cognitive functions, while inhibited hippocampal neuroinflammation demonstrated by decreased expression of NLRP3/caspase-1 axis, pro-inflammation cytokines and microglial activation. This study demonstrates for the first time that miR-138-5p suppresses the hippocampal NLRP3/caspase-1 signaling pathway activation in cognition impaired rats.Conclusion: The low expression of miR-138-5p after LPS administration may contribute to the activation of the NLRP3/caspase-1 pathway, leading to hippocampal neuroinflammation and cognitive impairment in rat models. These findings indicate a promising therapeutic avenue for cognitive disorders.Keywords: microRNA-138-5p, NLRP3/caspase-1, neuroinflammation, cognitive impairment, microglial activation

Abstract Background MicroRNAs (miRNAs) are implicated in the progression of ischemic stroke (IS) and bone marrow-derived mesenchymal stem cells (BMSCs)-derived exosomes play a role in IS therapy. Herein we hypothesized that the BMSCs-derived exosomes containing overexpressed miR-138-5p could protect the astrocytes following IS involved with lipocalin 2 (LCN2). Methods The differentially expressed gene related to IS was initially identified by bioinformatics analysis. miR-138-5p was predicted to regulate LCN2. The expression of miR-138-5p and LCN2 was altered in the oxygen-glucose deprivation (OGD)-induced astrocytes. Furthermore, the cell behaviors and inflammatory responses were evaluated both in astrocytes alone and astrocytes co-cultured with exosomes derived from BMSCs overexpressing miR-138-5p to explore the involvement of miR-138-5p and LCN2 in IS. Besides, middle cerebral artery occlusion (MCAO) mouse model was established to explore the effect of BMSCs-derived exosomal miR-138-5p in IS in vivo. Results LCN2 was highly expressed in IS. Besides, LCN2 was a target gene of miR-138-5p. BMSCs-derived exosomes could be endocytosed by astrocytes via co-culture. Overexpression of miR-138-5p promoted the proliferation and inhibited apoptosis of astrocytes injured by OGD, accompanied by the reduced expression of inflammatory factors, which was achieved by down-regulating LCN2. More importantly, BMSCs delivered miR-138-5p to the astrocytes via exosomes and BMSCs-derived exosomal miR-138-5p alleviated neuron injury in IS mice. Conclusion BMSCs-derived exosomal miR-138-5p reduces neurological impairment by promoting proliferation and inhibiting inflammatory responses of astrocytes following IS by targeting LCN2, which may provide a novel target for IS treatment.

Objective: Gastric cancer is one of the most common malignant tumors. Bruceine D (BD) is one of the extracts of Brucea javanica. In recent years, it has been reported that BD has anti-tumor activity in some human cancers through different mechanisms. Here, this study try to explore the effect of BD on gastric cancer and its regulatory mechanism.Methods: Cell proliferation ability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays, 5-bromo-2-deoxyuridine (BrdU) staining and soft agar colony formation assay, respectively. The tumor xenograft model was used to verify the effect of BD on the tumorigenicity of gastric cancer cells in vivo. Flow cytometry analysis and Western blot assay were performed to detect cell cycle and apoptosis. Gastric cancer cells were analyzed by transcriptome sequencing. The interaction between LINC01667, microRNA-138-5p (miR-138-5p) and Cyclin E1 was verified by dual luciferase experiment and RT-PCR assays.Results: We found that BD significantly inhibited cell proliferation and induced cell cycle arrest at S phase in gastric cancer cells. Transcriptome analysis found that the expression of a long non-coding RNA, LINC01667, were significantly down-regulated after BD treatment. Mechanically, it was discovered that LINC01667 upregulated the expression of Cyclin E1 by sponging miR-138-5p. Furthermore, BD enhanced the chemosensitivity of gastric cancer cells to doxorubicin, a clinically used anti-cancer agent.Conclusion: BD inhibit the growth of gastric cancer cells by downregulating the LINC01667/miR-138-5p/Cyclin E1 axis. In addition, BD enhances the chemosensitivity of gastric cancer cells to doxorubicin. This study indicates that BD may be used as a candidate drug for the treatment of patients with gastric cancer.

Although malignant glioblastoma (GBM) treatment has significantly improved in the past few decades, the prognosis of GBM remains unsatisfactory. MicroRNA (miR)-138-5p has been reported as a tumor suppressor in several types of human cancer; however, little is known about the function of miR-138-5p in GBM. The present study aimed to investigate the role of miR-138-5p in GBM as well as the underlying molecular mechanisms. The present study performed bioinformatics analysis, reverse transcription-quantitative (RT-q) PCR, western blotting, cell viability assays, colony formation assays, invasion assays and cell cycle analysis to investigate the biological function of miR-138-5p in both patient tissues and cell lines. In addition, miR-138-5p targets in GBM were predicted using Gene Expression Omnibus website and further validated by a dual luciferase reporter gene assay. The results revealed that miR-138-5p expression levels in patients with GBM from a Gene Expression Omnibus dataset were significantly downregulated. RT-qPCR analysis of miR-138-5p expression levels also revealed similar results in GBM tissues and cell lines. The upregulation of miR-138-5p expression levels using a mimic significantly inhibited the cell viability, colony formation and the G0/G1 to S progression in GBM cell lines, suggesting that miR-138-5p may be a tumor suppressor. Moreover, miR-138-5p was discovered to directly target cyclin D3 (CCND3), a protein that serves an important role in the cell cycle, and inhibited its expression. Finally, silencing CCND3 using small interfering RNA suppressed the viability of GBM cells. In conclusion, the results of the present study suggested that miR-138-5p may function as a tumor suppressor in GBM by targeting CCND3, indicating that miR-138-5p may be a novel therapeutic target for patients with GBM. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) play an important role in the development and progression of spinal cord injury (SCI). The role of miR-138-5p in SCI was investigated in the present study. The anti-inflammatory effects of miR-138-5p and underlying mechanisms were investigated in an SCI rat model and in vitro model. Reverse transcription-quantitative PCR (RT-qPCR) was used to examine the expression of miR-138-5p in the SCI in vivo and in vitro models, as well as patients with SCI; it was found that miR-138-5p was significantly upregulated in SCI. Bioinformatics and dual-luciferase reporter assays were performed to predict and confirm the binding sites between miR-138-5p and the 3′untranslated region of sirtuin 1 (SIRT1). Then, the expression of SIRT1 was detected via RT-qPCR and western blotting, indicating downregulation of SIRT1 in SCI. PC12 cells were transfected with miR-138-5p inhibitor, inhibitor control or miR-138-5p inhibitor + SIRT1 small interfering RNA for 48 h, and then subjected to lipopolysaccharide (100 ng/ml) treatment for 4 h. Then, MTT assay, flow cytometry and ELISA experiments were performed to analyze cell viability, apoptosis, and the levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6. Findings suggested that downregulation of miR-138-5p increased PC12 cell viability, inhibited cell apoptosis and attenuated proinflammatory responses, which may result in amelioration of SCI. However, all these effects were reversed by SIRT1 knockdown. Finally, it was observed that miR-138-5p altered the related protein expression of the PTEN/AKT pathway. These results indicated that miR-138-5p could regulate inflammatory responses and cell apoptosis in SCI models by modulating the PTEN/AKT signaling pathway via SIRT1, thus playing an important role in the development of SCI. Collectively, the present study demonstrated that miR-138-5p may be a novel therapeutic target for the treatment of SCI. [ABSTRACT FROM AUTHOR]

Dysregulation of microRNAs (miRNAs) is frequently observed during cancer development. Aberrant expression of miRNA-138-5p (miR-138-5p) has been found in many types of cancer. However, the role and the mechanisms underlying miR-138-5p function in non-small cell lung cancer (NSCLC) progression remain unknown. In the present study, miR-138-5p expression was identified to be decreased in tumor tissues compared with matched normal tissues from patients with NSCLC. In addition, low expression of miR-138-5p was detected in three NSCLC cell lines compared with a normal lung epithelium cell line. Moreover, CDK8 mRNA expression was increased in tumor tissues compared with matched normal tissues from patients with NSCLC, and an inverse association between miR-138-5p and CDK8 was observed. Furthermore, CDK8 was predicted to be a target of miR-138-5p. Dual luciferase assay confirmed that miR-138-5p could directly bind to the 3′ untranslated region of CDK8 mRNA. In A549 cells, overexpression of miR-138-5p inhibited cell growth and significantly increased cell apoptosis rates and the number of cells in G0/G1 phase. Moreover, forced overexpression of CDK8 partially reversed miR-138-5p mimic-induced cell growth arrest and alteration of cell apoptosis and cell cycle. In conclusion, the present results suggested that miR-138-5p may be a tumor suppressor in NSCLC cells and a promising therapeutic target for treating patients with NSCLC. [ABSTRACT FROM AUTHOR]

The distant metastasis in papillary thyroid carcinoma (PTC) is a major threat for PTC patients. Moreover, the involvement of long noncoding RNAs (lncRNAs) in the regulation of PTC progression has been extensively investigated. The aim of this study was to underscore whether lncRNA RP11‐476D10.1 affects the proliferation, apoptosis and autophagy of PTC cells. Initially, we determined that lncRNA RP11‐476D10.1 and LRRK2 were highly expressed in PTC cells. Meanwhile, through experimentation, miR‐138‐5p was confirmed to bind with lncRNA RP11‐476D10.1 and LRRK2. It was also revealed that lncRNA RP11‐476D10.1 downregulated the miR‐138‐5p expression, thereby upregulating the LRRK2 expression. After that, PTC cells were transfected with siRNA against RP11‐476D10.1, or inhibitor or mimic of miR‐138‐5p to evaluate the influence of lncRNA RP11‐476D10.1 on the PTC cell proliferation, apoptosis, and autophagy in vitro and on the tumor formation ability in vivo. The results showed that silenced lncRNA RP11‐476D10.1 or overexpressed miR‐138‐5p enhanced the apoptosis and autophagy of PTC cells while reducing cell proliferation, with increased levels of Bax, LC3B, and Beclin1 and decreased Bcl‐2 level were observed. The inhibitory role of silenced lncRNA RP11‐476D10.1 role in the PTC development was further verified by the reduced tumor formation ability in nude mice. Our results demonstrated that lncRNA RP11‐476D10.1 could bind to miR‐138‐5p and promote LRRK2 expression. Moreover, the silencing of lncRNA RP11‐476D10.1 may inhibit the development of PTC, highlighting a novel insight for the development of superior therapeutic targets for PTC treatment. [ABSTRACT FROM AUTHOR]

Abstract Background MiR-138-5p is regarded as a tumour suppressor in many cancers. Transforming growth factor beta (TGF-β) often acts as a tumor promotor at the late stages of human cancers. However, the function of miR-138-5p on lung adenocarcinoma cells induced by TGF-β remains to be further confirmed. Methods RT-qPCR was used to detect the expression of human lung adenocarcinoma tissues, adjacent normal tissues, and relative cell lines. When the lung adenocarcinoma cells A549 and H1299 were transfected with negative control (NC), miR-138-5p mimics and miR-138-5p inhibitor by lipofectamine3000 and treated with or without TGF-β1, the lung adenocarcinoma cell function was detected by Immunofluorescence, Western blotting (WB), cell counting Kit-8 (CCK8), colony formation, EdU, Wound-healing and Transwell assays. The relation between miR-138-5p and zinc finger E-box-binding homeobox 2 (ZEB2) was detected by RT-qPCR, WB, and Luciferase reporter assays. When ZEB2 was knocked down, the lung adenocarcinoma cell function was detected by WB, CCK8 and Transwell assays. Results The expression of miR-138-5p was decreased in lung adenocarcinoma tissues and cell lines. When treated with or without TGF-β1, overexpression of miR-138-5p suppressed EMT, proliferation and metastasis of A549 and H1299. ZEB2 was verified as the direct target of miR-138-5p. Downregulation of ZEB2 suppressed EMT, proliferation and metastasis of lung adenocarcinoma cell, which could be reversed by miR-138-5p inhibitor. Conclusions MiR-138-5p inhibits epithelial-mesenchymal transition, growth and metastasis of lung adenocarcinoma cells through targeting ZEB2. [ABSTRACT FROM AUTHOR]

The mechanism of manganism caused by manganese (Mn), an important environmental risk factor for Parkinson's disease, is still unclear. Recent evidence suggested that autophagy participated in neurodegenerative diseases, in which microRNA played a crucial role. However, roles of microRNA in the aberrant autophagy that occurs in neurodegenerative diseases remains controversial. In nervous system, miRNA‐138‐5p is highly expressed and plays a key role in regulating memory and axon regeneration. Importantly, we also found that miR‐138‐5p expression decreased significantly after SH‐SY5Y cells exposed to manganese chloride (MnCl2) in previous study. To explore the role of miR‐138‐5p in Mn‐induced autophagy, autophagy associated indicators were detected. And we found that MnCl2 could induce autophagic dysregulation and inhibit expression of miR‐138‐5p. While the levels of LC3‐II/LC3‐I, Beclin1, and p62, the number of autophagosome formation significantly decreased after miR‐138‐5p over‐expression, which demonstrated that miR‐138‐5p could clearly retard Mn‐induced autophagy. In additional, we found there were classical and evolutionarily conserved miR‐138‐5p binding sites in 3′‐UTR region of SIRT1, which was inhibited when overexpression of miR‐138‐5p. Therefore, it was speculated that elevated expression of SIRT1 may be resulted from inhibition of miR‐138‐5p after cells exposed to MnCl2. Finally, we found that SIRT1 inhibitor EX‐527 suppressed Mn‐induced autophagy as well as miR‐138‐5p, while the suppression was reversed by SIRT1‐specific activator SRT1720. These results indicated that overexpression of miR‐138‐5p suppressed Mn‐induced autophagy by targeting SIRT1. [ABSTRACT FROM AUTHOR]

Study Design: Clinical study., Objective: Our work was aimed at exploring the expression and clinical significance of microRNA-138-5p (miR-138-5p) and Transforming Growth Factor-beta 3 (TGF-β3) in peripheral blood of patients with ankylosing spondylitis (AS)., Methods: Forty-seven patients with AS were selected as the AS group, and the staging of the enrolled AS patients was based on the BASDAI score: <4 points were classified as the stable stage (stable group) and ≥4 points were classified as the active stage (active group). Forty-seven cases were selected from the same period of healthy physical examination in our hospital as the control group. miR-138-5p and TGF-β3 levels and disease activity factors in peripheral blood were measured in all patients., Results: Compared to healthy subjects, reduced miR-138-5p levels and increased TGF-β3 levels were found in AS patient. Even more, level of miR-138-5p was decreased and level of TGF-β3 was found to be increased in active disease stage of AS in comparison to inactive disease. Correlation analysis disclosed that miR-138-5p expression in peripheral blood of AS patients was negatively correlated with TGF-β3, HLA-B27, ESR, CRP, and BASDAI; serum TGF-β3 was positively correlated with HLA-B27, ESR, CRP, and BASDAI. The ROC curve analysis disclosed that miR-138-5p and TGF-β3 had certain diagnostic value for AS, and the combined detection could improve the clinical diagnostic capability of this disease., Conclusion: miR-138-5p and TGF-β3 in peripheral blood of AS patients are potential biological markers for the diagnosis of AS and are expected to be new clinical diagnostic indicators., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The present study investigated the role of microRNA (miR)-138-5p in regulating carcinoma migration and sensitivity to chemotherapy in pancreatic cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression levels of miR-138-5p in pancreatic cancer cell lines and primary carcinoma tissues from human patients. A lentiviral vector, containing miR-138-5p mimics (lv-miR-138-m) or miR-138-5p inhibitor (lv-miR-138-i), was used to either upregulate or downregulate the expression levels of miR-138-5p in PANC-1 cells, respectively. The effects of miR-138-3p regulation on pancreatic cancer cell migration and sensitivity to chemotherapy were examined. The predicted targeting of miR-138-5p on vimentin (VIM) was assessed by western blotting in PANC-1 cells. VIM was subsequently downregulated using small interfering (si)RNA to determine its effect on miR-138-5p-modulated pancreatic cancer cell development. The expression levels of miR-138-5p were downregulated in pancreatic cancer cell lines and primary carcinoma tissues. In PANC-1 cells, lentivirus-mediated upregulation of miR-138-5p inhibited cancer cell migration and increased cell chemosensitivity to 5-fluorouracil (5-FU). By contrast, downregulation of miR-138-5p promoted cancer cell migration and decreased cell chemosensitivity to 5-FU. A luciferase assay revealed that VIM was a direct target of miR-138-5p. Western blotting demonstrated that VIM was downregulated upon the upregulation of miR-138-5p in PANC-1 cells. siRNA-mediated downregulation of VIM inhibited pancreatic cancer cell migration in the control and miR-138-5p downregulated PANC-1 cells. The present study demonstrated that miR-138-5p is important in regulating pancreatic cancer development, possibly through targeting VIM. [ABSTRACT FROM AUTHOR]

Asthma is a chronic airway inflammatory disease. The present study aimed to explore the effect of the long non-coding RNA taurine-upregulated gene 1 (TUG1) on the viability and migration of airway smooth muscle cells (ASMCs) in asthma. Rat asthma models were constructed with ovalbumin sensitization and challenge and the level of serum immunoglobulin E (IgE) and the rates of inspiratory and expiratory resistance were measured. Reverse transcription-quantitative PCR was also performed to determine the expression levels of TUG1. Platelet-derived growth factor-BB (PDGF-BB)-treated ASMCs were then used as a cell model of asthma. The viability and migratory abilities of ASMCs were analysed with the MTT and Transwell assays. Additionally, a dual-luciferase reporter assay was used to confirm the relationship between TUG1 and microRNA (miR)-138-5p and between transcription factor E2F3 and miR-138-5p. The expression of TUG1, level of serum IgE, inspiratory resistance and expiratory resistance were clearly increased in the rat asthma model in comparison with controls. Knockdown of TUG1 the viability and migration of PDGF-BB-induced ASMCs and reduced the inspiratory and expiratory resistances. In addition, TUG1 functioned as a bait of miR-138-5p, and miR-138-5p modulated E2F3 expression. Knockdown of E2F3 hindered the abnormal growth of ASMCs. Moreover, miR-138-5p inhibition or E2F3 overexpression reversed the inhibitory effects of TUG1 knockdown on viability and migration of PDGF-BB-induced ASMCs. The TUG1/miR-138-5p/E2F3 regulatory axis appeared to play a critical role in accelerating the viability and migration of ASMCs and may therefore have a role in asthma. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) cells-derived exosomes could mediate angiogenesis of human microvascular endothelial cells (HUVECs) in PC. Considering that, this research was implemented to figure out the concrete role of PC cells-derived exosomal long non-coding RNA colon cancer-associated transcript-1 (CCAT1) in PC with its regulation on microRNA-138-5p/high mobility group A1 (miR-138-5p/HMGA1) axis. PC tissues and normal tissues were resected. PC cells (PANC-1) were interfered with plasmids to change CCAT1 and/or miR-138-5p expression. Exosomes were isolated from PANC-1 cells and co-cultured with HUVECs. The proliferation and apoptosis of PANC-1 and HUVECs were examined. The angiogenic ability of HUVECs was tested in vivo in xenografted tumors and in vitro. CCAT1, miR-138-5p and HMGA1 expression were determined, as well as their interactions. CCAT1 and HMGA1 expression were raised while miR-138-5p expression was reduced in PC. Silencing CCAT1 disrupted cell proliferation and stimulated apoptosis of PANC-1 cells. Knocked down CCAT1 from PANC-1 cells-derived exosomes promoted apoptosis and repressed proliferation of HUVECs. Down-regulated/up-regulated CCAT1 from PANC-1 cells-derived exosomes destroyed/enhanced the angiogenic ability of HUVECs in vivo and in vitro. CCAT1 mediated HMGA1 through competitively binding to miR-138-5p. Overexpression of miR-138-5p antagonized the effects of up-regulated CCAT1 on angiogenesis of HUVECs in vitro. It is informative that PANC-1 cells-derived exosomal CCAT1 strengthens angiogenesis of HUVECs through binding to miR-138-5p to elevate HMGA1 expression. [ABSTRACT FROM AUTHOR]

Glioma is the most common type of primary brain cancer in adults. Accumulating studies have reported that long non-coding RNAs (lncRNAs) serve a significant role in the initiation and development of glioma. lncRNA small nucleolar RNA host gene 7 (SNHG7) has been previously demonstrated to serve a role in numerous glioma biological processes, including cell proliferation, invasion and migration. The present study aimed to investigate the role of SNHG7 in glioma through reverse transcription-quantitative PCR, western blotting and cell function assays. The results revealed that SNHG7 expression was upregulated in glioma tissues and cell lines, while microRNA (miR)-138-5p expression was downregulated. Moreover, the knockdown of SNHG7 expression decreased the proliferation of glioma cells. Mechanistic studies demonstrated that SNHG7 downregulated miR-138-5p expression, which subsequently affected the expression levels of its target gene, enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2). In conclusion, the results of the present study suggested that SNHG7 may act as a competing endogenous RNA to sponge miR-138-5p and modulate EZH2 expression. Thus, SNHG7 may enhance glioma proliferation via modulating the miR-138-5p/EZH2 signaling axis. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the regulatory effects of microRNA-138-5p (miR-138-5p) and sirtuin 1 (SIRT1) on the progression of heart failure (HF). The binding association between miR-138-5p and SIRT1 was assessed by the dual-luciferase reporter assay. By conducting reverse transcription-quantitative polymerase chain reaction and Western blotting, relative levels of SIRT1 and p53 regulated by miR-138-5p were detected. In vitro HF models were generated by hydrogen peroxide (H2O2) induction in AC-16 and human cardiomyocyte (HCM) cells, followed by detection of the regulatory effects of SIRT1 on cell apoptosis and p53 expression. MiR-138-5p was negatively correlated with the SIRT1 level in cardiomyocytes. By recognizing and specifically targeting SIRT1 3′-untranslated region (3′-UTR), miR-138-5p decreased the translational level of SIRT1 and inhibited its enzyme activity, thereby decreasing the deacetylation level of p53. Through downregulating SIRT1 and activating p53 signaling, miR-138-5p induced apoptosis in H2O2-induced AC-16 and HCM cells. By contrast, knockdown of miR-138-5p in the in vitro HF models significantly protected the cardiomyocytes. SIRT1 contributed toward alleviate HF by inhibiting cardiomyocyte apoptosis via enhancing the deacetylation level of p53. MiR-138-5p decreases the enzyme activity of SIRT1 by specifically targeting its 3′-UTR and activates p53 signaling, followed by triggering cardiomyocyte apoptosis during the process of HF. It is considered that miR-138-5p and SIRT1 may be potential diagnostic biomarkers and therapeutic targets for HF. [ABSTRACT FROM AUTHOR]

Long non‑coding RNAs (lncRNAs) and microRNAs (miRNAs) are essential for the progression of tumors, including cutaneous squamous cell carcinoma (CSCC). The present study aimed to examine the competing endogenous RNA (ceRNA) network in CSCC. Differentially expressed genes in CSCC were analyzed using the GSE66359 microarray data set, and the upstream miRNAs and lncRNAs were predicted using online database analysis (TargetScan 7.1, mirDIP 4.1, miRSearch V3.0, miRDB and RNA22 2.0) and were verified in clinical tissues. RNA pull‑down and dual luciferase reporter gene assays were used to verify the targeting relationships among lncRNA human histocompatibility leukocyte antigen complex P5 (HCP5), miR‑138‑5p and enhancer of zeste homolog 2 (EZH2). Cell lines with a high and low HCP5 expression were screened, and a pcDNA‑3.1‑HCP5 overexpression vector, small interfering RNA against HCP5, miR‑138‑5p mimics and miR‑138‑5p inhibitors were transfected into the CSCC cells. Cell viability, invasion, migration, apoptotic rate and autophagy were evaluated. The effects of HCP5 on autophagy and apoptosis of CSCC cells were verified in vivo using Ki67 and TUNEL staining. EZH2 was demonstrated to be upregulated in CSCC cells. miR‑138‑5p target sequences were identified in HCP5 and EZH2. HCP5 was revealed to function as a putative ceRNA of miR‑138‑5p to positively regulate EZH2, and EZH2 was shown to regulate autophagy and apoptosis of CSCC cells through the STAT3/VEGFR2 pathway. HCP5 overexpression decreased miR‑138‑5p levels, increased EZH2 levels and promoted cell malignant behaviors and autophagy but decreased the apoptosis rate. These trends were opposite when HCP5 was silenced. In conclusion, HCP5 may competitively bind to miR‑138‑5p to regulate EZH2 in CSCC cells, promoting autophagy and reducing apoptosis through the STAT3/VEGFR2 pathway. This study may provide a new perspective for understanding the molecular mechanism and treatment of CSCC.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Concern was raised about the reliability of the Western blot results in Figs. 2B and 5I+J, which appear to have the same eyebrow shaped phenotype as many other publications tabulated here (https://docs.google.com/spreadsheets/d/149EjFXVxpwkBXYJOnOHb6RhAqT4a2llhj9LM60MBffM/edit#gid=0). In addition, Fig. 4B appears to show a digital composition of xenografted tumors. The journal requested the corresponding author comment on these concerns and provide the raw data. However the authors were not able to satisfactorily fulfil this request and therefore the Editor-in-Chief decided to retract the article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Gastric cancer is one of the most common malignant tumors. Bruceine D (BD) is one of the extracts of Brucea javanica. In recent years, it has been reported that BD has anti-tumor activity in some human cancers through different mechanisms. Here, this study try to explore the effect of BD on gastric cancer and its regulatory mechanism. Methods: Cell proliferation ability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays, 5-bromo-2-deoxyuridine (BrdU) staining and soft agar colony formation assay, respectively. The tumor xenograft model was used to verify the effect of BD on the tumorigenicity of gastric cancer cells in vivo. Flow cytometry analysis and Western blot assay were performed to detect cell cycle and apoptosis. Gastric cancer cells were analyzed by transcriptome sequencing. The interaction between LINC01667, microRNA-138-5p (miR-138-5p) and Cyclin E1 was verified by dual luciferase experiment and RT-PCR assays. Results: We found that BD significantly inhibited cell proliferation and induced cell cycle arrest at S phase in gastric cancer cells. Transcriptome analysis found that the expression of a long non-coding RNA, LINC01667, were significantly down-regulated after BD treatment. Mechanically, it was discovered that LINC01667 upregulated the expression of Cyclin E1 by sponging miR-138-5p. Furthermore, BD enhanced the chemosensitivity of gastric cancer cells to doxorubicin, a clinically used anti-cancer agent. Conclusion: BD inhibit the growth of gastric cancer cells by downregulating the LINC01667/miR-138-5p/Cyclin E1 axis. In addition, BD enhances the chemosensitivity of gastric cancer cells to doxorubicin. This study indicates that BD may be used as a candidate drug for the treatment of patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Rationale: Differential activation of macrophages correlates closely with tumor progression, and the epigenetic factor lysine demethylase 6B (KDM6B, previously named JMJD3) mediates the regulation of macrophage polarization through an unknown mechanism. Methods: We developed a suspension coculture system comprising breast cancer cells and macrophages and used RT-qPCR and western blotting to measure KDM6B expression. Bioinformatics and luciferase reporter assays were used to identify candidate microRNAs of cancer cells responsible for the downregulation of KDM6B. To determine if exosomes mediated the transfer of miR-138-5p between cancer cells to macrophages, we treated macrophages with exosomes collected from the conditioned medium of cancer cells. The effects of exosomal miR-138-5p on macrophage polarization were measured using RT-qPCR, flow cytometry, and chromatin immunoprecipitation assays. We employed a mouse model of breast cancer, metastatic to the lung, to evaluate the effects on tumor metastasis of macrophages treated with miR-138-5p-enriched exosomes. To develop a diagnostic evaluation index, the levels of exosomal miR-138-5p in samples from patients with breast cancer were compared to those of controls. Results: Coculture of breast cancer cells led to downregulation of KDM6B expression in macrophages. Cancer cell-derived exosomal miR-138-5p inhibited M1 polarization and promoted M2 polarization through inhibition of KDM6B expression in macrophages. Macrophages treated with exosomal miR-138-5p promoted lung metastasis, and the level of circulating exosomal miR-138-5p positively correlated with the progression of breast cancer. Conclusion: Our data suggest that miR-138-5p was delivered from breast cancer cells to tumor-associated macrophages via exosomes to downregulate KDM6B expression, inhibit M1 polarization, and stimulate M2 polarization. Therefore, exosomal miR-138-5p represents a promising prognostic marker and target for the treatment of breast cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Although malignant glioblastoma (GBM) treatment has significantly improved in the past few decades, the prognosis of GBM remains unsatisfactory. MicroRNA (miR)-138-5p has been reported as a tumor suppressor in several types of human cancer; however, little is known about the function of miR-138-5p in GBM. The present study aimed to investigate the role of miR-138-5p in GBM as well as the underlying molecular mechanisms. The present study performed bioinformatics analysis, reverse transcription-quantitative (RT-q)PCR, western blotting, cell viability assays, colony formation assays, invasion assays and cell cycle analysis to investigate the biological function of miR-138-5p in both patient tissues and cell lines. In addition, miR-138-5p targets in GBM were predicted using Gene Expression Omnibus website and further validated by a dual luciferase reporter gene assay. The results revealed that miR-138-5p expression levels in patients with GBM from a Gene Expression Omnibus dataset were significantly downregulated. RT-qPCR analysis of miR-138-5p expression levels also revealed similar results in GBM tissues and cell lines. The upregulation of miR-138-5p expression levels using a mimic significantly inhibited the cell viability, colony formation and the G 0 /G 1 to S progression in GBM cell lines, suggesting that miR-138-5p may be a tumor suppressor. Moreover, miR-138-5p was discovered to directly target cyclin D3 (CCND3), a protein that serves an important role in the cell cycle, and inhibited its expression. Finally, silencing CCND3 using small interfering RNA suppressed the viability of GBM cells. In conclusion, the results of the present study suggested that miR-138-5p may function as a tumor suppressor in GBM by targeting CCND3, indicating that miR-138-5p may be a novel therapeutic target for patients with GBM., (Copyright: © Wu et al.)

Parkinson's disease (PD) is a common neurodegenerative disease. Various microRNAs (miRNAs) have been reported to play important roles in cell growth regulation and inflammatory reaction. However, the detailed roles of miR-217 and miR-138-5p in PD progression remain to be investigated. In the present study, we explored the effects and underlying mechanisms of miR-217 and miR-138-5p on the inflammatory response, oxidative stress and the induction of neuronal apoptosis in an in vitro PD cell line model induced by 1-methyl-4-phenylpyridinium (MPP + ). The results of the biological software analysis and luciferase reporter assays demonstrated that sirtuin 1 (SIRT1) was a direct target of miR-217 and miR-138-5p. MiR-217 and miR-138-5p exhibited a negative regulatory effect on the expression of SIRT1 in SH-SY5Y cells. In addition, the expression levels of miR-217 and miR-138-5p were increased, and SIRT1 expression was decreased in SH-SY5Y cells following MPP + treatment. Loss-of-function experiments indicated that treatment of the cells with inhibitors against miR-217 and miR-138-5p promoted cell viability and superoxide dismutase (SOD) activity, while the induction of cell apoptosis, lactate dehydrogenase (LDH) activity, and the reactive oxygen species (ROS) release were inhibited in MPP + -induced SH-SY5Y cells. Moreover, the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were reduced in MPP + -induced SH-SY5Y cells. Treatment of the cells with the miR-217 and the miR-138-5p inhibitors significantly inhibited the ratio of phosphorylated (p)-p65/p65 expression levels in MPP + -induced SH-SY5Y cells. In summary, the present study demonstrated that the miR-217/miR-138-5p/SIRT1 axis was involved in the progression of PD by regulating the inflammatory response and the induction of oxidative stress and neuronal apoptosis. The data provide new diagnostic and therapeutic strategies for PD patients., Competing Interests: None., (AJTR Copyright © 2019.)

The mechanism of manganism caused by manganese (Mn), an important environmental risk factor for Parkinson's disease, is still unclear. Recent evidence suggested that autophagy participated in neurodegenerative diseases, in which microRNA played a crucial role. However, roles of microRNA in the aberrant autophagy that occurs in neurodegenerative diseases remains controversial. In nervous system, miRNA-138-5p is highly expressed and plays a key role in regulating memory and axon regeneration. Importantly, we also found that miR-138-5p expression decreased significantly after SH-SY5Y cells exposed to manganese chloride (MnCl 2 ) in previous study. To explore the role of miR-138-5p in Mn-induced autophagy, autophagy associated indicators were detected. And we found that MnCl 2 could induce autophagic dysregulation and inhibit expression of miR-138-5p. While the levels of LC3-II/LC3-I, Beclin1, and p62, the number of autophagosome formation significantly decreased after miR-138-5p over-expression, which demonstrated that miR-138-5p could clearly retard Mn-induced autophagy. In additional, we found there were classical and evolutionarily conserved miR-138-5p binding sites in 3'-UTR region of SIRT1, which was inhibited when overexpression of miR-138-5p. Therefore, it was speculated that elevated expression of SIRT1 may be resulted from inhibition of miR-138-5p after cells exposed to MnCl 2 . Finally, we found that SIRT1 inhibitor EX-527 suppressed Mn-induced autophagy as well as miR-138-5p, while the suppression was reversed by SIRT1-specific activator SRT1720. These results indicated that overexpression of miR-138-5p suppressed Mn-induced autophagy by targeting SIRT1., (© 2019 Wiley Periodicals, Inc.)

Colorectal cancer (CRC) is the second most common cancer in the world. The incidence of this cancer is increasing in the developing countries. Mechanism of CRC tumorigenesis has been widely studied at the molecular levels, and has been recently proposed microRNAs as novel players in CRC. It has been reported that microRNA-138-5p (miR-138-5p) play key roles in different kinds of human cancers. However, the roles and underlying molecular mechanisms of miR-138-5p in CRC have not been adequately elucidated. Thus, the aim of the present study was to investigate the roles and possible regulatory mechanisms of miR-138-5p in CRC. In this study, we demonstrated that miR-138-5p was significantly down-regulated in CRC tissue samples and cell lines. Functional analyses indicated that the overexpression of miR-138-5p significantly delayed cell proliferation, reduced colony formation and increased apoptosis in CRC cell lines. Moreover, human telomerase reverse transcriptase (hTERT), an important oncogene in the management of tumors, was confirmed as a direct target of miR-138-5p in CRC cells. We also found that the hTERT expression was increased in CRC tissues and was inversely correlated with miR-138-5p. Further study showed that the restoration of hTERT expression by an overexpressing plasmid could reverse the effects of miR-138-5p on proliferation and apoptosis of CRC cells. Taken together, these data defines a major suppresses proliferation and promotes apoptosis role for miR-138-5p, a microRNA functions as a tumor suppressor in CRC, by directly targeting hTERT, which would be provide a new strategy for future CRC therapies., Competing Interests: None., (IJCEP Copyright © 2017.)