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Objective To observe the effects of Fusobacterium nucleatum and microRNA-497(miR-497) on the proliferation, invasion and migration of colorectal cancer cells, and to analyze their regulatory relationships. Methods Colorectal cancer cell line HCT116 was transfected with miR-497 overexpression plasmid miR-497 mimic and was randomly divided into the infection index (MOI) 100 group, MOI 200 group, MOI 500 group, and MOI 1 000 group. They were co-cultured with Fusobacterium nucleatum with MOI of 100, 200, 500 and 1 000, respectively. Real-time fluorescent quantitative PCR was used to detect miR-497 in each group. The treatment concentration of the bacteria with the lowest expression of miR-497 was selected as the subsequent action concentration of Fusobacterium nucleatum. HCT116 cells were randomly divided into the control group, miR-497 over-expression group, miR-497 down-expression group, miR-497 over-expression negative control group and miR-497 down-expression negative control group, respectively. Cells in the control group were cultured without treatment. Cells in the miR-497 over-expression group, miR-497 down-expression group, over-expression negative control group, and down-expression negative control group were transfected with miR-497 mimics, miR497 inhibitor, mimic NC, and inhibitor NC, respectively, by Lipofectamine 2000. Cell proliferation ability was observed by CCK-8 assay, cell invasion ability was observed by Transwell assay, and cell migration ability was observed by Scratch healing assay. HCT116 cells were randomly divided into the control group, miR-497 over-expression group, overexpression negative control group, and over-expression + Fusobacterium nucleatum group, respectively. Cells in the control group were cultured without treatment, and cells in the miR-497 over-expression group were transfected with miR-497 mimic, while cells in the over-expression negative control group were transfected with mimic NC. After transfecting miR-497 mimic, cells in the overexpression + Fusobacterium nucleatum group were co-cultured with selected concentration of Fuso⁃ bacterium nucleatum. The cell proliferation ability was observed by CCK-8 assay, the cell invasion ability was observed by Transwell assay, and the cell migration ability was observed by Scratch healing assay. Results The miR-497 expression was as follows: MOI 100 group >MOI 200 group >MOI 500 group >MOI 1 000 group (all P<0. 05), and MOI 1 000 was selected as the subsequent action concentration of Fusobacterium nucleatum. Cell proliferation rate, the number of invasive cells and migration rate were as follows： miR-497 down-expression group > control group, overexpression negative control group, down-expression negative control group > miR-497 over-expression group (all P<0. 05). Cell proliferation rate, the number of invasive cells, and migration rate were as follows: miR-497 overexpression group < overexpression + Fusobacterium nucleatum group < control group, overexpression negative control group (all P<0. 05). Conclusion Fusobacterium nucleatum can promote the proliferation, invasion and migration of colorectal cancer cells through negative regulation of miR-497. [ABSTRACT FROM AUTHOR]

Recently, extracellular vesicles (EVs) have been emphasized in regulating the hypoxic tumor microenvironment of breast cancer (BC), where tumor‐associated fibroblasts (TAFs) play a significant role. In this study, we describe possible molecular mechanisms behind the pro‐tumoral effects of EVs, secreted by hypoxia (HP)‐induced TAFs, on BC cell growth, metastasis, and chemoresistance. These mechanisms are based on long noncoding RNA H19 (H19) identified by microarray analysis. We employed an in silico approach to identify differentially expressed lncRNAs that were associated with BC. Subsequently, we explored possible downstream regulatory mechanisms. We isolated EVs from TAFs that were exposed to HP, and these EVs were denoted as HP‐TAF‐EVs henceforth. MTT, transwell, flow cytometry, and TUNEL assays were performed to assess the malignant phenotypes of BC cells. A paclitaxel (TAX)‐resistant BC cell line was constructed, and xenograft tumor and lung metastasis models were established in nude mice for in vivo verification. Our observation revealed that lncRNA H19 was significantly overexpressed, whereas miR‐497 was notably downregulated in BC. HP induced activation of TAFs and stimulated the secretion of EVs. Coculture of HP‐TAF‐EVs and BC cells led to an increase in TAX resistance of the latter. HP‐TAF‐EVs upregulated methylation of miR‐497 by delivering lncRNA H19, which recruited DNMT1, thus lowering the expression of miR‐497. In addition, lncRNA H19‐containing HP‐TAF‐EVs hindered miR‐497 expression, enhancing tumorigenesis and TAX resistance of BC cells in vivo. Our study presents evidence for the contribution of lncRNA H19‐containing HP‐TAF‐EVs in the reduction of miR‐497 expression through the recruitment of DNMT1, which in turn promotes the growth, metastasis, and chemoresistance of BC cells. [ABSTRACT FROM AUTHOR]

Abstract Background Abnormal DNA methylation of tumor suppressor gene promoter has been found in breast cancer. Therefore, the current study set out to explore how DNA methyltransferase 1 (DNMT1) affects breast cancer through mediating miR-497/GPRC5A axis. Methods After loss and gain-of-function approaches were conducted in MCF-7/ADR and MCF-7 cells, cell viability, IC50 value, invasion, migration and apoptosis were measured, respectively. In addition, drug resistance, metastasis and apoptosis-related protein expression were examined using immunoblotting. ChIP and dual-luciferase reporter gene assays were carried out to validate relationship among DNMT1, miR-497, and GPRC5RA. Subcutaneous xenograft tumor model in nude mice was established to detect effects of DNMT1 on growth and metastasis of breast cancer in vivo. Results It was found that DNMT1 was notably increased, while miR-497 was poorly-expressed in breast cancer. Highly-expressed DNMT1 could promote chemotherapy resistance and metastasis of breast cancer. Meanwhile, DNMT1 modified methylation of CpG island in miR-497 promoter region, thereby repressing miR-497 level. In addition, miR-497 targeted GPRC5A expression to curb chemotherapy resistance and metastasis of breast cancer cells. Lastly, in vivo experiments showed that knockdown of DNMT1 could suppress breast cancer growth and metastasis. Conclusions Collectively, our findings indicated that DNMT1 may inhibit miR-497 and boost the expression of GPRC5A through methylation, thus augmenting breast cancer chemotherapy resistance and metastasis, which provides novel mechanistic insight into the unrecognized roles of DNMT1 in breast cancer.

Aberrant expression of microRNA‐497 (miR‐497) is associated with tumor progression, but the molecular mechanisms in tumorigenesis remain largely unknown. Here, we report that miR‐497 expression is downregulated in esophageal squamous cell carcinoma (ESCC) clinical samples. Consistently, upregulation of miR‐497 inhibits ESCC cell malignant properties and tumor growth in vivo. Importantly, we uncovered that miR‐497 upregulation suppressed ESCC cell growth and tumor growth by inhibiting Smurf2. Mechanistically, we showed that Smurf2 was a target of miR‐497, and mediated YY1 expression to elevate HIF2α expression, thereby enhancing the malignancy of ESCC cells. Together, our study uncovered the role of the miR‐497‐mediated Smurf2/YY1/HIF2α axis in tumor growth and metastasis, which might provide potential therapeutic targets for human ESCC. [ABSTRACT FROM AUTHOR]

PurposeMicroRNA-497 (miR-497) is previously reported to target fibroblast growth factor 23 (FGF-23) and regulates cardiac injury, while their value in predicting drug-induced cardiotoxicity is not reported. Thus, the current study aimed to investigate the correlation of miR-497/FGF-23 with neoadjuvant/adjuvant trastuzumab-induced cardiotoxicity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients.MethodsA total of 97 HER2-positive surgical breast cancer patients who received neoadjuvant/adjuvant trastuzumab contained regimens were enrolled; then, their peripheral blood mononuclear cells (PBMC) and serum were collected at baseline, after neoadjuvant treatment, at 3 months (M3), 6 months (M6), 9 months (M9), and 12 months (M12) after surgery. The PBMC was used for miR-497 measurements, and the serum was used for FGF-23 measurements. The cardiotoxicity events and incidence were recorded.ResultsA total of 24 (24.7%) patients occurred cardiotoxicity during the treatment period. MiR-497 decreased from baseline (median: 0.955) to M12 after surgery (median: 0.602) (p

Background: Abnormal DNA methylation of tumor suppressor gene promoter has been found in breast cancer. Therefore, the current study set out to explore how DNA methyltransferase 1 (DNMT1) affects breast cancer through mediating miR-497/GPRC5A axis. Methods: After loss and gain-of-function approaches were conducted in MCF-7/ADR and MCF-7 cells, cell viability, IC50 value, invasion, migration and apoptosis were measured, respectively. In addition, drug resistance, metastasis and apoptosis-related protein expression were examined using immunoblotting. ChIP and dual-luciferase reporter gene assays were carried out to validate relationship among DNMT1, miR-497, and GPRC5RA. Subcutaneous xenograft tumor model in nude mice was established to detect effects of DNMT1 on growth and metastasis of breast cancer in vivo. Results: It was found that DNMT1 was notably increased, while miR-497 was poorly-expressed in breast cancer. Highly-expressed DNMT1 could promote chemotherapy resistance and metastasis of breast cancer. Meanwhile, DNMT1 modified methylation of CpG island in miR-497 promoter region, thereby repressing miR-497 level. In addition, miR-497 targeted GPRC5A expression to curb chemotherapy resistance and metastasis of breast cancer cells. Lastly, in vivo experiments showed that knockdown of DNMT1 could suppress breast cancer growth and metastasis. Conclusions: Collectively, our findings indicated that DNMT1 may inhibit miR-497 and boost the expression of GPRC5A through methylation, thus augmenting breast cancer chemotherapy resistance and metastasis, which provides novel mechanistic insight into the unrecognized roles of DNMT1 in breast cancer. [ABSTRACT FROM AUTHOR]

ObjectiveSerum microRNAs (miRNAs) may serve as biomarkers in various cancers. Our study aims to explore the roles of miR-497 and miR-1246 in hepatocellular carcinoma (HCC).MethodsThe expression levels of miR-497 and miR-1246 were measured by RT-PCR. A correlation analysis was conducted between the expression levels of miR-497 and miR-1246 and clinicopathological characteristics of patients. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic efficacy in HCC. In addition, bioinformatics tools were also utilized to predict the potential targets of miR-497 and miR-1246.ResultsThe expression level of miR-497 in HCC was significantly down-regulated compared with the control group while the miR-1246 revealed a significantly higher expression level in HCC. There was a significant correlation demonstrated between the expression levels of miR-497 and miR-1246 in preoperative serum of HCC and the differentiation degree, Tumor Node Metastasis (TNM) classification, and metastasis. The expression levels of serum miR-497 and miR-1246 were significantly associated with the diagnosis, prognosis, and overall survival rate of patients with HCC. Moreover, the potential target genes of miR-497 in HCC include ARL2, UBE2Q1, PHF19, APLN, CHEK1, CASK, SUCO, CCNE1, and KIF23. The low expression of these nine genes is associated with a better prognosis of HCC patients. AUTS2 is a novel target gene of miR-1246, and its low expression is significantly related to the low overall survival rate of HCC patients.ConclusionsmiR-497 and miR-1246 are possibly involved in the progression of HCC by regulating target genes, respectively, and could serve as biomarkers in HCC.

Objective: Serum microRNAs (miRNAs) may serve as biomarkers in various cancers. Our study aims to explore the roles of miR-497 and miR-1246 in hepatocellular carcinoma (HCC). Methods: The expression levels of miR-497 and miR-1246 were measured by RT-PCR. A correlation analysis was conducted between the expression levels of miR-497 and miR-1246 and clinicopathological characteristics of patients. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic efficacy in HCC. In addition, bioinformatics tools were also utilized to predict the potential targets of miR-497 and miR-1246. Results: The expression level of miR-497 in HCC was significantly down-regulated compared with the control group while the miR-1246 revealed a significantly higher expression level in HCC. There was a significant correlation demonstrated between the expression levels of miR-497 and miR-1246 in preoperative serum of HCC and the differentiation degree, Tumor Node Metastasis (TNM) classification, and metastasis. The expression levels of serum miR-497 and miR-1246 were significantly associated with the diagnosis, prognosis, and overall survival rate of patients with HCC. Moreover, the potential target genes of miR-497 in HCC include ARL2, UBE2Q1, PHF19, APLN, CHEK1, CASK, SUCO, CCNE1, and KIF23. The low expression of these nine genes is associated with a better prognosis of HCC patients. AUTS2 is a novel target gene of miR-1246, and its low expression is significantly related to the low overall survival rate of HCC patients. Conclusions: miR-497 and miR-1246 are possibly involved in the progression of HCC by regulating target genes, respectively, and could serve as biomarkers in HCC. [ABSTRACT FROM AUTHOR]

BackgroundPotential anti-tumor effects of microRNA-497 (miR-497) have been highlighted in various malignancies including breast cancer. However, little is known about the function of miR-497 and its putative target mucin1 (MUC1) in breast cancer. The present study explored how miR-497 regulates breast cancer progression in a MUC1-dependent manner.MethodsExpression of miR-497 and MUC1 was determined in breast cancer tissues and cells. Methylation specific polymerase chain reaction was used to measure the methylation status of CpG islands of miR-497 promoter, while chromatin immunoprecipitation assay was used to detect recruitment of methyltransferase to the promoter region of miR-497. Alteration in expression of miR-497 (overexpression) and MUC1 (up- and down-regulation) was performed to examine their roles in breast cancer biology in vitro and in vivo. The binding affinity between miR-497 and MUC1 was investigated through a bioinformatics database and dual luciferase reporter gene assay.ResultsMiR-497 was down-regulated and MUC1 was up-regulated in breast cancer tissues and cell lines. Besides, methylation induced a down-regulation of miR-497 in breast cancer. The bioinformatics analysis and dual luciferase reporter gene assay indicated that miR-497 targeted MUC1. Overexpression of miR-497 inhibited breast cancer cell proliferation and invasion and promoted the apoptosis of breast cancer cells by down-regulating MUC1. The inhibitory action of miR-497 on tumor growth was validated in vivo.ConclusionIn conclusion, miR-497 down-regulated MUC1 expression and subsequently suppressed breast cancer progression, highlighting miR-497 to be a potential biomarker and therapeutic target for breast cancer therapy.

MicroRNAs (miRNAs) have been corroborated to engage in the process of cellular activities in osteoporosis. However, few researches have been conducted to expose the integrated role of miR‐497, leucine‐rich alpha‐2‐glycoprotein‐1 (LRG1) and transforming growth factor beta 1 (TGF‐β1)/Smads signalling pathway in osteoporosis. Thereafter, the study is set out to delve into miR‐497/LRG1/TGF‐β1/Smads signalling pathway axis in osteoporosis. Osteoporosis bone tissues and normal bone tissues were collected. Rat osteoporosis models were constructed via ovariectomy. Model rats were injected with restored miR‐497 or depleted LRG1 to explore their roles in osteoporosis. Rat osteoblasts were extracted from osteoporosis rats and transfected with restored miR‐497 or depleted LRG1 for further verification. MiR‐497 and LRG1 expression in femoral head tissues and osteoblasts of osteoporosis rats were detected. TGF‐β1/Smads signalling pathway‐related factors were detected. MiR‐497 was poorly expressed while LRG1 was highly expressed and TGF‐β1/Smads signalling pathway activation was inhibited in osteoporosis. MiR‐497 up‐regulation or LRG1 down‐regulation activated TGF‐β1/Smads signalling pathway, promoted collagen type 1 synthesis and suppressed oxidative stress in femoral head tissues in osteoporosis. MiR‐497 restoration or LRG1 knockdown activated TGF‐β1/Smads signalling pathway, promoted viability and suppressed apoptosis of osteoblasts in osteoporosis. Our study suggests that miR‐497 up‐regulation or LRG1 down‐regulation promotes osteoblast viability and collagen synthesis via activating TGF‐β1/Smads signalling pathway, which may provide a novel reference for osteoporosis treatment. [ABSTRACT FROM AUTHOR]

Background: Potential anti-tumor effects of microRNA-497 (miR-497) have been highlighted in various malignancies including breast cancer. However, little is known about the function of miR-497 and its putative target mucin1 (MUC1) in breast cancer. The present study explored how miR-497 regulates breast cancer progression in a MUC1-dependent manner. Methods: Expression of miR-497 and MUC1 was determined in breast cancer tissues and cells. Methylation specific polymerase chain reaction was used to measure the methylation status of CpG islands of miR-497 promoter, while chromatin immunoprecipitation assay was used to detect recruitment of methyltransferase to the promoter region of miR-497. Alteration in expression of miR-497 (overexpression) and MUC1 (up- and down-regulation) was performed to examine their roles in breast cancer biology in vitro and in vivo. The binding affinity between miR-497 and MUC1 was investigated through a bioinformatics database and dual luciferase reporter gene assay. Results: MiR-497 was down-regulated and MUC1 was up-regulated in breast cancer tissues and cell lines. Besides, methylation induced a down-regulation of miR-497 in breast cancer. The bioinformatics analysis and dual luciferase reporter gene assay indicated that miR-497 targeted MUC1. Overexpression of miR-497 inhibited breast cancer cell proliferation and invasion and promoted the apoptosis of breast cancer cells by down-regulating MUC1. The inhibitory action of miR-497 on tumor growth was validated in vivo. Conclusion: In conclusion, miR-497 down-regulated MUC1 expression and subsequently suppressed breast cancer progression, highlighting miR-497 to be a potential biomarker and therapeutic target for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Exercise training (ET) could improve myocardial infarction (MI), and microRNA-497 is highly associated with MI. This study aimed to investigate whether the regulation of miR-497 is involved in the positive effects of ET on MI. MI rat models induced by left anterior descending (LAD) were subjected to interval training and infarct size was observed. Blood and myocardial samples were collected from the rats for determining the expressions of miR-497. To evaluate the functions of miR-497, miR-497 agomir and antagomir were injected accordingly into grouped rats during ET, and subsequently, the expressions of apoptotic and inflammatory factors were determined. ET reduced the infarct size in MI rats and inhibited the levels of miR-497. MiR-497 agomir injection enlarged the infarct size, and reversed the shrunk infarct size induced by ET. However, miR-497 antagomir further promoted the positive effect on MI improved by ET. Chloride voltage-gated channel 3 (CLCN3) was identified as the most possible target for miR-497. Moreover, ET improving MI also involved the regulation of apoptotic and inflammatory factors. The mechanisms underlying the positive effects of ET on MI were highly associated with the regulation of miR-497. [ABSTRACT FROM AUTHOR]

Introduction: Long non-coding RNAs (lncRNAs) have obtained increasing attention due to their regulatory functions in many cancers. This work aimed to investigate the functional roles of lncRNA TTN-AS1 in colorectal cancer (CRC) and to explore the underlying mechanisms. Methods: The expression profiles of TTN-AS1 and miR-497 in CRC tissues and cell lines were determined by RT-qPCR analysis. MTT assay, transwell assay, western blot analysis, and xenograft tumors in nude mice were employed to analyze the effects of TTN-AS1 on the proliferation, migration, invasion, EMT, and in vivo tumorigenesis of CRC cells. Bioinformatics analysis and dual-luciferase reporter assay determined the direct binding relation between TTN-AS1 and miR-497 in CRC. Results: We observed a significant increase of TTN-AS1 expression level in CRC tissues and cell lines compared with normal counterparts. High expression of TTN-AS1 predicted a poor prognosis and was correlated with aggressive clinicopathological characteristics in CRC patients. Functionally, gain- and loss-of-function studies indicated that TTN-AS1 knockdown suppressed the proliferation, migration, invasion and epithelial–mesenchymal transition of CRC cells in vitro, whereas TTN-AS1 overexpression showed the complete opposite effects. Mechanistically, we found that TTN-AS1 could directly interact with miR-497, and co-transfection with miR-497 mimics blocked the activation of PI3K/Akt/mTOR signaling, and reversed the effects of TTN-AS1 overexpression in CRC cells. Conclusion: To conclude, our findings provide novel insight into CRC tumorigenesis and indicate that TTN-AS1 may serve as a potential therapeutic target for CRC treatment. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor receptor 1 (FGFR1) signaling has been reported to contribute to the carcinogenic progression of various cancer types. Previous studies have demonstrated that FGFR1 expression is increased in non-small cell lung cancer (NSCLC) and promotes cancer cell metastasis. However, the molecular mechanisms underlying increased FGFR1 expression in NSCLC remains largely unknown. In the current study, microRNA (miR)-497 levels were observed to be inversely correlated with FGFR1 expression in tumor samples from patients with NSCLC. In the NSCLC cell line A549, miR-497 overexpression inhibited cell proliferation and migration. Increased expression of miR-497 led to a reduction in FGFR1 expression, at the mRNA and protein levels. In addition, transfection of miR-497 mimics inactivated the protein kinase B (AKT) and c-Jun N-terminal kinase (JNK) signaling pathways, as reduced matrix metallopeptidase 26 expression; all of which are regulated by FGFR1. Using TargetScan software, FGFR1 was also identified as a predicted target gene of miR-497, and a dual luciferase reporter assay confirmed that miR-497 directly regulated FGFR1. Transfection of a recombinant FGFR1 overexpression vector reversed miR-497 mimic-induced arrest of cell growth and migration in A549 cells. In conclusion, the results of the present study identified miR-497 as a potential tumor suppressor gene in NSCLC that may function via repressing FGFR1 expression, and AKT and JNK signaling. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) function as oncogenes or tumor suppressors in human cancers by targeting mRNAs for degradation and/or translational repression. miR‐497 has been proposed as a tumor suppressive miRNA and its deregulation is observed in human cancers. However, the prognostic value of miR‐497 and its underlying molecular pathways involved in the initiation and development of hepatocellular carcinoma (HCC) are poorly investigated. In the present study, we found that the mean level of miR‐497 in HCC tissues was lower than that in adjacent nontumor tissues. Clinical data indicated that low expression of miR‐497 was prominently associated with adverse prognostic features of HCC including high serum alpha‐fetoprotein (AFP) level, large tumor size, high Edmondson–Steiner grading and advanced tumor–node–metastasis (TNM) stage. Furthermore, miR‐497 was an independent prognostic factor for indicating both 5‐year overall survival and disease‐free survival of HCC patients. Gain‐ and loss‐of‐function studies showed that miR‐497 reduced cell proliferation and induced apoptosis in HCC cells. Yes‐associated protein 1 (YAP1) was identified as a direct target of miR‐497 in HCC. An inverse correlation between YAP1 and miR‐497 expression was observed in HCC tissues. Notably, YAP1 knockdown abrogated the effects of miR‐497 deletion on HCC cells with decreased cell proliferation and increased apoptosis. In conclusion, we report that miR‐497 is a potent prognostic indicator and may suppress tumor growth of HCC by targeting YAP1.

Background: Down-expression of microRNA-497 (miR-497) was often found in malignancies. The purposes of this study were to determine the expression of miR-497 in human osteosarcoma and to establish the association between miR-497 expression with cell survival and the sensitivity to cisplatin in human osteosarcoma cells. Methods: The effects of ectopic miR-497 expression on the cell survival and cisplatin sensitivity in osteosarcoma cells were measured by the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression of miR-497. The effects of ectopic miR-497 expression on the expression of VEGFA, Akt and p-Akt were determined by western blot. Results: Real-time quantitative PCR analysis revealed that miR-497 was significantly down-regulated in osteosarcoma tissues and in the osteosarcoma cell line SAOS-2 compared with adjacent nontumorous osteosarcoma tissues and normal human osteoblasts. Up-regulation of miR-497 inhibited cell survival and enhanced the sensitivity to cisplatin in osteosarcoma cells. In addition, knockdown of miR-497 induced osteosarcoma cells growth and cisplatin resistance. Luciferase reporter assay and western blot confirmed that VEGFA was a direct target of miR-497. PI3K inhibitor LY294002 abrogated miR-497 inhibitors induced cisplatin resistance. Conclusion: Taken together, our results suggest that miR-497 modulates the sensitivity to cisplatin at least in part through PI3K/Akt pathway in osteosarcoma cells.

Highlights • circPVT1 is overexpressed in NSCLC. • Knockdown of circPVT1 inhibits NSCLC cell proliferation and induces NSCLC cell apoptosis. • Knockdown of circPVT1 inhibits NSCLC tumor growth. • circPVT1 acts as a ceRNA for miR-497 in NSCLC cells. • Inhibition of miR-497 abrogates the effects of circPVT1 knockdown in NSCLC cells. Abstract Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and play crucial regulatory roles in human cancer biology. The purpose of the present study was to explore the expression pattern and biological role of circular RNA PVT1 (circPVT1) in non-small cell lung cancer (NSCLC). We firstly found that circPVT1 was overexpressed in clinical NSCLC tissues and cell lines. NSCLC patients with high expression of circPVT1 exhibited aggressive clinicopathological characteristics and poor prognosis. In vitro assays of the NSCLC cell lines (H1299 and A549 cells) demonstrated that knockdown of circPVT1 inhibited NSCLC cell proliferation and induced NSCLC cell apoptosis. We further found that circPVT1 served as a competing endogenous RNA of miR-497 and indirectly regulated Bcl-2 expression in NSCLC cells. Finally, inhibition of miR-497 abrogated the effects of circPVT1 knockdown in NSCLC cells. Taken together, the results from our study indicated circPVT1 acts as an oncogene in NSCLC, and may serve as a promising therapeutic target for NSCLC patients. [ABSTRACT FROM AUTHOR]

Abstract Gastric cancer (GC) is the most common gastrointestinal malignancy in the digestive system. Recent studies have proven that long non-coding RNAs (lncRNAs) are closely related to tumor growth and metastasis. The study aimed to explore the effect of LINC00978 on GC cells proliferation and tumorigenesis. LINC00978 was up-regulated in GC tissues and cell lines. Up-regulation of LINC00978 was positively correlated with low survival rate. LINC00978 silence inhibited proliferation, metastasis, and promoted apoptosis in BGC-823 cells. Additionally, LINC00978 functioned as competing endogenous RNA to inhibit miR-497 expression. Further, NTRK3 was confirmed as a target gene of miR-497. Up-regulation of NTRK3 was found in GC tissues, and the positive correlation was presented between LINC00978 and NTRK3. Further, LINC00978 promoted cell proliferation and tumor weight by regulation of NTRK3. These findings demonstrated that LINC00978 promoted cell proliferation and tumorigenesis by regulating miR-497/NTRK3 axis in GC. Highlights • LINC00978 is up-regulated in GC, and associated with short overall survival of GC patients. • LINC00978 silencing inhibits cell proliferation, metastasis, and induces apoptosis. • The relationship of reciprocal repression is presented between LINC00978 and miR-497. • NTRK3 is a target gene of miR-497. • LINC00978 promotes cell proliferation and tumorigenesis by regulating NTRK3. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a cancer that occurs in plasma cells, which fall under the category of white blood cells that are in charge of antibody production. According to previous studies, microRNA-497 (miR-497) functions as a tumor suppressor in several types of cancer, including gastric cancer and colorectal cancer. Therefore, the present study aims to investigate the effects of miR-497 on cellular function of human MM cells through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway by targeting Raf-1. The differentially expressed genes and miRs in MM, and the relationship between the miR and gene were verified. It was found that Raf-1 was a target gene of miR-497. The data obtained from MM tissues showed increased Raf-1 level and decreased miR-497 level. MM cells were treated with mimic, inhibitor and siRNA in order to evaluate the role of miR-497, Raf-1 and MAPK/ERK in MM. The expression pattern of miR-497, Raf-1, ERK1/2, survivin, B-cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) as well as the extent of ERK1/2 phosphorylation were determined. Retored miR-497 and si-Raf-1 resulted in increases in the Bax expression and cell apoptosis and decreases in the expressions of Raf-1, MEK-2, survivin, Bcl-2, along with the extent of ERK1/2 phosphorylation. In addition, the biological function evaluations of MM cells revealed that miR-497 mimic or si-Raf-1 led to suppression in cell proliferation, invasion and migration. In conclusion, our results have demonstrated that miR-497 targets Raf-1 in order to inhibit the progression of MM by blocking the MAPK/ERK signaling pathway. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore the various modes of action miR‐497 has on human cervical cancer (CC) cell behavior. We also speculate that miR‐497 achieves its anti‐tumor role by governing RAF‐1 via MAPK/ERK signaling pathway. CC tissues with corresponding adjacent normal tissues were collected from 168 CC patients. RAF‐1‐positive cells were identified by means of immunohistochemistry in tissues. A series of inhibitors, mimics and siRNA against RAF‐1 were introduced to validate regulatory mechanisms for miR‐497 and RAF‐1. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot assay were employed for evaluating alternations of miR‐497, RAF‐1, and MAPK/ERK signaling pathway. HeLa cell proliferation, invasion, migration, cycle progression, and apoptosis were assessed by means of CCK‐8, wound‐healing, transwell invasion assays, and flow cytometry, respectively. The target prediction program and luciferase activity determination were used to identify miR‐497 targeting RAF‐1. We determined reduced miR‐497 expression and elevated expression of RAF‐1 in CC tissues as opposed to adjacent tissues. Transfection of miR‐497 mimics and siRNA‐RAF‐1 both decreased levels of MEK1, ERK1, and p38 phosphorylation in HeLa cells, inhibited cell proliferation, migration and invasion, induced more cells arrested in the G0/G1 phase, and promoted cell apoptosis; while miR‐497 inhibitors led to opposite results. These findings indicate miR‐497 as a tumor suppressor results from negative regulation of the MAPK/ERK signaling pathway via RAF‐1 in CC. [ABSTRACT FROM AUTHOR]

Introduction Myocardial ischemia-reperfusion (I/R) injury affects millions of people worldwide and has a very high mortality rate. Since microRNA-497 (miR-497) has been found to be related with cardiomyocyte apoptosis, this study aimed to explore the effect of miR-497 by targeting Mfn2 in a mouse model of myocardial ischemia-reperfusion (I/R) injury. Materials BALB/c mice were modeled with I/R and some were injected with miR-497 agomir before I/R to observe whether miR-497 alleviates the injury that occurs as a result of I/R. Bioinformatics website and dual-luciferase reporter gene assay were employed in order to detect the relations between miR-497 and Mfn2 gene. Next, cells were extracted to be transfected with different mimic, inhibitor and siRNAs to further explore how miR-497 acts to I/R. Western blot analysis and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were conducted to measure expressions of miR-497, Mfn2, Fas, Bcl-2, Bax and Caspase-3 in myocardial tissues and cardiomyocytes after transfection. CCK-8 assay and flow cytometry were used to determine proliferation, cell cycle distribution and apoptosis of cardiomyocytes in each group after transfection. Results Mice with I/R had myocardial dysfunction but before the injection with miR-497 agomir, the impairment was alleviated. Mfn2 was verified as the target gene of miR-497. The inhibition of miR-497 in turn inhibits Mfn2 expressione and cardiomyocyte apoptosis. The overexpression of miR-497 and Mfn2 gene silencing can lead to the promotion of proliferation capability of mice cardiomyocytes in vitro. Overexpressed miR-497 and Mfn2 gene silencing can also facilitate cell cycle entry and inhibit the apoptosis cardiomyocytes of mice in vitro. Conclusion The present study provided strong evidence that miR-497 promotes proliferation and inhibits apoptosis of cardiomyocytes by downregulating the expression of Mfn2 in a mouse model of myocardial I/R injury. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have been demonstrated to serve an important role in diverse biological processes and cancer progression. Downregulation of microRNA‑497 (miR‑497) has been observed in human colorectal cancer (CRC) tissues, but the function of miR‑497 in CRC has not been well investigated. In the present study, it was demonstrated that expression of miR‑497 was significantly downregulated in human CRC tissues compared to adjacent normal tissues. Enforced expression of miR‑497 inhibited proliferation, migration and invasion abilities of CRC cell lines SW1116 and SW480. Furthermore, overexpression of miR‑497 inhibited phosphoinositide 3‑kinase/AKT and mitogen‑activated protein kinase/extracellular signal‑regulated kinase signaling by targeting insulin receptor substrate 1 (IRS1). In human clinical specimens, IRS1 was inversely correlated with miR‑497 in CRC tissues. Collectively, the results of the present study demonstrate that miR‑497 is a tumor suppressor miRNA and indicate its potential application for the treatment of human CRC in the future. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common tumor of the endocrine organs. Emerging studies have indicated the critical roles of microRNAs (miRs) in papillary thyroid cancer (PTC) formation and progression through function as tumor suppressors or oncogenes. The present study investigated the expression level and biological roles of miR‑497 in PTC and its underlying mechanisms. It was demonstrated that the expression level of miR‑497 was reduced in both PTC tissues and cell lines. Enforced expression of miR‑497 suppressed PTC cell proliferation, migration and invasion. According to bioinformatics analysis, a luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blotting, RAC‑γ serine/threonine‑protein kinase (AKT3) was demonstrated to be the direct target gene of miR‑497. In addition, AKT3 expression increased in PTC tissues and negatively correlated with miR‑497 expression. Furthermore, downregulation of AKT3 also suppressed cell proliferation, migration and invasion of PTC, which had similar roles to miR‑497 overexpression in PTC cells. Taken together, these results suggested that this newly identified miR‑497/AKT3 signaling pathway may contribute to PTC occurrence and progression. These findings provide novel potential therapeutic targets for the therapy of PTC. [ABSTRACT FROM AUTHOR]

Previous studies have reported the crucial role of microRNAs (miRNAs) in the biology and tumorigenesis of various types of cancer, including bladder cancer. The present study aimed to investigate the importance of miRNA (miR)-497 on the pathogenesis of bladder cancer. A total of 50 patients diagnosed with bladder cancer were enrolled in the current study. The expression levels of miR-497 in the cancerous and the adjacent noncancerous tissues were detected using reverse transcription-quantitative polymerase chain reaction. The association between miR-497 expression and various parameters, including age, tumor-node-metastasis (TNM) stage and pathological classification was determined. An miR-497-overexpressing vector was transfected into the T24 and BIU-87 bladder cancer cell lines in order to determine the effect of miR-497 expression on cell migration and invasion using Transwell assays. Additionally, the cell migration and invasion-associated protein expression levels were also analyzed using western blotting. The findings of the present study revealed that miR-497 was expressed at low levels in the cancer bladder tissue compared with the adjacent noncancerous tissue, and its expression was associated with the pathological classification, TNM stage and metastasis. Additionally, miR-497 overexpression significantly reduced the number of migrated and invasive T24 and BIU-87 cells. The mRNA and protein expression levels of E-cadherin were increased, whereas levels of vimentin and a-smooth muscle actin were reduced following miR-497 overexpression. The present study revealed that miR-497 overexpression may be a suppressor of the metastasis of bladder cancer, and may have an important role in the diagnosis of bladder cancer. [ABSTRACT FROM AUTHOR]

The expression level and roles of microRNA-497 (miR-497) have been frequently reported in previous studies on cancer. However, its expression, function and associated molecular mechanisms in retinoblastoma remain unknown. In the present study, miR-497 expression levels in human retinoblastoma tissues, normal retinal tissues and retinoblastoma cell lines were determined using reverse transcription-quantitative polymerase chain reaction. In addition, a Cell Counting Kit-8 assay, cell migration assay, cell invasion assay, western blot analysis and Dual-Luciferase reporter assay were used to explore the expression, functions and molecular mechanisms of miR-497 in human retinoblastoma. It was demonstrated that miR-497 was significantly downregulated in retinoblastoma tissues and cell lines compared with normal retinal tissues. Ectopic expression of miR-497 decreased the proliferation, migration and invasion of retinoblastoma cells. Furthermore, VEGFA was verified as a potential direct target of miR-497 in vitro. Taken together, the results indicate that miR-497 functions as a tumor suppressor in the carcinogenesis and progression of retinoblastoma via targeting VEGFA. miR-497 should be investigated as a potential therapeutic target for the treatment of retinoblastoma. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effects of microRNA (miRNA/miR)-497 expression levels on the expression levels of synuclein γ (SNCG) in serum samples, as well as osteosarcoma and lung-metastatic tissue samples, from patients with osteosarcoma. Between December 2010 and August 2013, fasting peripheral blood was collected from 36 patients with osteosarcoma for serum separation. In addition, osteosarcoma and lung metastatic tissues were resected from 15 osteosarcoma patients with lung metastasis by surgery. Bioinformatics was employed to predict the amount miRNA that binds to SNCG. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression levels of SNCG and miR-497, and western blotting was performed to determine protein expression levels. It was observed that SNCG mRNA and protein expression levels were significantly upregulated in osteosarcoma tissues (P<0.01). Additionally, SNCG mRNA (P<0.01) and protein (P<0.05) expression levels were significantly upregulated in the blood of patients with osteosarcoma. SNCG mRNA and protein expression levels were also significantly upregulated in lung metastatic tissues (P<0.01). miR-497 was significantly downregulated in all three samples; therefore downregulation of miR-497 may lead to the occurrence, development and metastasis of osteosarcoma through the upregulation of SNCG mRNA. In summary, the upregulation of SNCG in blood, osteosarcoma tissue and lung metastatic tissue samples is associated with the dowregulation of miR-497, suggesting that miR-497 may be a potential marker and therapeutic target for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the effect of baicalin on the expression of miR-497 and its target B-cell lymphoma-2 (Bcl-2) in the hippocampus of kainic acid (KA)-induced epileptic mice. To establish status epilepticus (SE), 0.1 µg/5 µl KA was injected into the lateral cerebral ventricle in mice, which then received an intraperitoneal injection of baicalin (100 mg/kg) after 1 and 8 h. Hematoxylin and eosin staining was used to observe the pathological changes in morphology and neuronal apoptosis was determined by terminal transferase-mediated dUTP nick end-labeling staining. Western blot analysis was used to detect the expression of Bcl-2 and cleaved caspase-3 proteins in the hippocampus, while reverse transcription-quantitative polymerase chain reaction was used to quantify hippocampal miR-497 expression. The results showed that baicalin significantly attenuated neuronal damage and apoptosis in the hippocampus 72 h after SE. In addition, baicalin decreased SE-induced expression of miR-497 and cleaved caspase-3 protein, while upregulating the expression of Bcl-2 protein. In conclusion, the present results suggest that baicalin possesses potent antiapoptotic properties and attenuates hippocampal injury in mice after SE, which may be associated with the downregulation of miR-497 and cleaved caspase-3 and the upregulation of Bcl-2. [ABSTRACT FROM AUTHOR]

The expression and function of microRNA-497 (miR-497) has previously been reported in various types of human cancer; however, miR-497 has not previously been investigated in human osteosarcoma (OS). In the present study, the expression levels of miR-497 were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in OS tissues and cell lines. In addition, post-transfection with miR-497, RT-qPCR, cell proliferation, migration and invasion assays, western blot analysis, and luciferase assays were performed in OS cell lines. The results of the present study demonstrated that miR-497 was downregulated in OS tissues and cells compared with normal controls. Furthermore, upregulation of miR-497 inhibited cell proliferation, migration and invasion in osteosarcoma cell lines compared with the negative control group. In addition, the present study demonstrated that miR-497 may function by directly targeting insulin-like growth factor 1 receptor in OS cells. These findings indicated that miR-497 may be useful as a therapeutic target for the treatment of OS. [ABSTRACT FROM AUTHOR]

MicroRNA-497 (miR-497) has been reported to be downregulated in certain types of cancer, including breast, gastric, endometrial, colorectal and prostate cancer as well as hepatocellular and nasopharyngeal carcinoma. The present study aimed to investigate the underlying mechanism of the tumor suppressor function of miR-497 in prostate cancer. Following transfection with miR-497, the DU145 and PC-3 prostate cancer cell lines were subjected to Transwell migration and invasion assays, western blot analysis and a luciferase assay. It was revealed that miRNA-497 inhibited the migration and invasion of prostate cancer cells. In addition, is was indicated that miRNA-497 directly targets hepatoma-derived growth factor (HDGF) in prostate cancer cells. These results suggested that restoration of miR-497 and the resulting downregulation of HDFG may represent a promising therapeutic strategy for prostate cancer. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. MicroRNA-497 (miR-497) is known to be downregulated in several types of human cancer; however, the expression, function and underlying mechanisms of miR-497 in HCC remain unclear. Therefore, the present study investigated miR-497 expression in HCC samples and HCC-derived cell lines using reverse transcription-quantitative polymerase chain reaction. The protein expression of one of the predicted common targets of miR-497, insulin-like growth factor-1 receptor (IGF-1R), was assessed using western blot analyses and immunohistochemistry. The role of miR-497 in regulating the proliferation of HCC-derived cells was also investigated in vitro and in vivo. Of 60 paired specimens from HCC patients, miR-497 was downregulated in 42 cancer specimens compared with adjacent non-cancer tissues. Western blotting and immunohistochemical analyses revealed that IGF-1R expression was significantly increased in HCC compared to control tissues. In addition, overexpression of miR-497 was observed to inhibit colony formation and tumor growth in MHCC-97H human HCC cells. Conversely, SMMC-7721 human HCC cells transfected with a miR-497 inhibitor exhibited enhanced colony formation and tumor growth. Finally, IGF-1R protein, phosphoinositide 3-kinase/Akt signaling pathway-associated proteins and cyclin pathway-associated proteins were differentially expressed between miR-497-overexpressing cells and miR-497-silenced cells. These results indicate that miR-497 may be a potentially effective gene therapy target. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) function as oncogenes or tumor suppressors in human cancers by targeting mRNAs for degradation and/or translational repression. miR‐497 has been proposed as a tumor suppressive miRNA and its deregulation is observed in human cancers. However, the prognostic value of miR‐497 and its underlying molecular pathways involved in the initiation and development of hepatocellular carcinoma (HCC) are poorly investigated. In the present study, we found that the mean level of miR‐497 in HCC tissues was lower than that in adjacent nontumor tissues. Clinical data indicated that low expression of miR‐497 was prominently associated with adverse prognostic features of HCC including high serum alpha‐fetoprotein (AFP) level, large tumor size, high Edmondson–Steiner grading and advanced tumor–node–metastasis (TNM) stage. Furthermore, miR‐497 was an independent prognostic factor for indicating both 5‐year overall survival and disease‐free survival of HCC patients. Gain‐ and loss‐of‐function studies showed that miR‐497 reduced cell proliferation and induced apoptosis in HCC cells. Yes‐associated protein 1 (YAP1) was identified as a direct target of miR‐497 in HCC. An inverse correlation between YAP1 and miR‐497 expression was observed in HCC tissues. Notably, YAP1 knockdown abrogated the effects of miR‐497 deletion on HCC cells with decreased cell proliferation and increased apoptosis. In conclusion, we report that miR‐497 is a potent prognostic indicator and may suppress tumor growth of HCC by targeting YAP1. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have a role in the development and progression of human malignancy. The expression of miR-497 is decreased in malignant tumors, which suggests a role for miR-497 as a tumor suppressor. Angiomotin is encoded by the AMOT gene, which is a target for miR-497. Angiomotin has a role in angiogenesis, cell proliferation, and invasion in human malignancies, including osteosarcoma. However, the role of miR-497 in human osteosarcoma is unknown. This preliminary study included human osteosarcoma tissues and normal tissues from 20 patients, the osteosarcoma cell lines, MG-63, SAOS-2, U-2 OS, and the human osteoblast cell line hFOB (OB3). Western blots for angiomotin and quantitative real-time polymerase chain reaction for the expression of miR-497 and AMOT were performed. Knockdown studies were performed using RNA interference and transfection studies used miR-497 mimics. Quantitative cell migration assays were performed, and cell apoptosis was studied by flow cytometry. Osteosarcoma cells and cell lines showed reduced expression of miR-497 and increased expression of angiomotin. Transfection of osteosarcoma cells with miR-497 mimics suppressed the expression of angiomotin. Results from a dual-luciferase reporter system supported AMOT as a direct target gene of miR-497. Knockdown of AMOT using RNA interference resulted in inhibition of osteosarcoma cell proliferation, migration, and invasion. These preliminary studies support a role for miR-497 as a suppressor of AMOT gene expression in human osteosarcoma cells, resulting in suppression of tumor cell proliferation and invasion. Further studies are recommended to investigate the role of miR-497 in osteosarcoma and other malignant mesenchymal tumors. [ABSTRACT FROM AUTHOR]

Background: Down-expression of microRNA-497 (miR-497) was often found in malignancies. The purposes of this study were to determine the expression of miR-497 in human osteosarcoma and to establish the association between miR-497 expression with cell survival and the sensitivity to cisplatin in human osteosarcoma cells. Methods: The effects of ectopic miR-497 expression on the cell survival and cisplatin sensitivity in osteosarcoma cells were measured by the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression of miR-497. The effects of ectopic miR-497 expression on the expression of VEGFA, Akt and p-Akt were determined by western blot. Results: Realtime quantitative PCR analysis revealed that miR-497 was significantly down-regulated in osteosarcoma tissues and in the osteosarcoma cell line SAOS-2 compared with adjacent nontumorous osteosarcoma tissues and normal human osteoblasts. Up-regulation of miR- 497 inhibited cell survival and enhanced the sensitivity to cisplatin in osteosarcoma cells. In addition, knockdown of miR-497 induced osteosarcoma cells growth and cisplatin resistance. Luciferase reporter assay and western blot confirmed that VEGFA was a direct target of miR- 497. PI3K inhibitor LY294002 abrogated miR-497 inhibitors induced cisplatin resistance. Conclusion: Taken together, our results suggest that miR-497 modulates the sensitivity to cisplatin at least in part through PI3K/Akt pathway in osteosarcoma cells. [ABSTRACT FROM AUTHOR]

Objective Dysregulation of microRNAs (miRNAs) plays critical roles in tumor progression. The aim of this study was to investigate the clinicopathologic and prognostic significance of miR-497 expression in human breast cancer (BC). Methods Taqman qRT-PCR assay was performed to detect the expression of microRNA (miR)-497 in 30 pairs of BC tissues and corresponding noncancerous breast tissues. Additionally, the expression of this miRNA was detected in another 128 BC tissues and its correlations with clinicopathologic features of patients were analyzed. Kaplan-Meier analyses were used to assess survival of patients. Univariate and multivariate analyses were performed using the Cox proportional hazards model to analyze the prognostic significance of miR-497 expression. Results Our data indicated that the relative level of miR-497 expression in BC tissues was significantly lower than that in corresponding noncancerous breast tissues (P = 0.0046). Of 128 BC patients, 74 (57.8%) were placed in the high-miR-497 group and 54 (42.2%) were placed in the low-miR-497 group. By statistical analyses, low miR-497 expression was observed to be closely correlated with higher differentiation grade, positive HER-2 expression, higher incidence of lymph node metastasis and advanced clinical stage. Moreover, patients with high miR-497 expression had better 5-year disease-free and overall survival compared with the low miR-497 group (P = 0.0124 and 0.0018, respectively). Univariate and multivariate analyses indicated that low miR-497 expression was an independent poor prognostic factor for BC patients. Conclusions Our data provided the first evidence that downregulation of miR-497 was correlated with BC progression, and miR-497 might be a potential molecular biomarker for predicting the prognosis of patients. [ABSTRACT FROM AUTHOR]

Drug resistance is a major problem to overcome in the treatment of cancer; therefore, identifying therapeutic targets for drug resistance is a point of focus in the field of cancer research. Long non-coding RNAs (lncRNAs) and microRNAs (miRs) not only affect gene expression regulation during cell proliferation, but also have several potential roles in the drug resistance of malignant tumors. Reverse transcription-quantitative PCR was used to detect the expression levels of DDX11 antisense RNA 1 (DDX11-AS1) and miR-497 in MCF-7 and MDA-MB-231 cells. Cell transfection techniques were used to interfere with the expression levels of DDX11-AS1 and miR-497. Cell Counting Kit-8 and MTT assays were used to detect cell viability. A colony formation assay was used to detect cell proliferation. Wound-healing and Transwell assays were performed to measure the levels of cell migration and invasion. Western blotting was used to analyze the expression levels of migration-associated proteins, and immunofluorescence and western blotting were used to determine the expression levels of the epithelial-mesenchymal transition-related proteins E-cadherin and N-cadherin, respectively. A luciferase reporter gene assay was used to verify the targeted binding of DDX11-AS1 and miR-497. The present study demonstrated that the expression levels of lncRNA DDX11-AS1 were markedly increased in paclitaxel (PTX)-resistant breast cancer cell lines. By contrast, knockdown of DDX11-AS1 expression inhibited PTX resistance of breast cancer cells, and suppressed the proliferation, invasion and migration of breast cancer cells, which was achieved via upregulation of miR-497 expression. In conclusion, knockdown of lncRNA DDX11-AS1 could inhibit the proliferation, migration and PTX resistance of breast cancer cells by upregulating miR-497 expression. [ABSTRACT FROM AUTHOR]

Objectives: Cancer stem cells (CSCs) comprise a small population of cells in cancerous tumors and play a critical role in tumor resistance to chemotherapy. miRNAs have been reported to enhance the sensitivity of pancreatic cancer to chemotherapy. However, the underlying molecular mechanism requires better understanding., Methods: Cell viability and proliferation were examined with CCK8 assays. Quantitative real-time polymerase chain reaction was executed to assess mRNA expression. StarBase database was used to select the target genes of miRNA, which were further affirmed by dual luciferase assay. Transwell assay was used to analyze cell invasion and migration., Results: We proved that miR-497 could be obviously downregulated in pancreatic cancer tissues and CSCs from Aspc-1 and Bxpc-3 cells. In addition, inhibition of miR-497 evidently accelerated pancreatic CSC gemcitabine resistance, migration and invasion. Moreover, we revealed that nuclear factor kappa B 1 (NFκB1) was prominently upregulated in pancreatic cancer tissues and pancreatic CSCs, and NFκB1 was also identified as a direct target of miR-497. Furthermore, we demonstrated that overexpression of NFκB1 could also notably promote the viability, migration, and invasion of gemcitabine-treated pancreatic CSCs, but this effect could be partially abolished by miR-497 overexpression., Conclusions: Those findings suggest that miR-497 overexpression could suppress gemcitabine resistance and the metastasis of pancreatic CSCs and non-CSCs by directly targeting NFκB1.

MicroRNA (miR)-497 has been reported as a tumor suppressor in various cancer types. Nonetheless, the regulation of triple-negative breast cancer (TNBC) by miR-497 remains poorly understood. The present study aimed to investigate the potential function and mechanism of miR-497 in TNBC. A total of 36 TNBC and matched non-cancerous tissue samples were collected for analysis. Reverse transcription-quantitative PCR was performed to detect the miR-497 levels in TNBC tissue. The association between miR-497 expression, clinical characteristics and survival was then analyzed. To investigate the role of miR-497 in TNBC, MTT, colony formation, Transwell invasion, cell cycle and cell apoptosis assays were conducted following transfection of miR-497 mimics into the MDA-MB-231 and MDA-MB-468 cell lines. Luciferase reporter assays and western blot analysis were used to confirm the regulation of a putative target of miR-497. The results indicated that the expression of miR-497 was downregulated in the TNBC specimens. Further analysis demonstrated that the expression of miR-497 was downregulated in patients with advanced TNBC stages and that low miR-497 was associated with poor prognosis in patients with TNBC. Transfection of miR-497 mimics inhibited TNBC cell proliferation and increased cell apoptosis in MDA-MB-231 and MDA-MB-468 cells. Moreover, cell migration was inhibited following overexpression of miR-497, which also led to the arrest of the breast cancer cells in the G0/G1 phase of the cell cycle. Yes-associated protein 1 (YAP1), a critical molecule in the Hippo pathway, was identified as a target of miR-497. Notably, the protein and mRNA expression levels of YAP1 in MDA-MB-231 and MDA-MB-468 cells were downregulated following overexpression of miR-497. Overall, the findings of the present study indicated that miR-497 inhibited TNBC cell proliferation and migration and induced cell apoptosis by negatively regulating YAP1 expression. Thus, targeting miR-497 may represent a potential strategy for the treatment of TNBC. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs/miRs) are a type of non-coding single-stranded RNA, with a length of ~22 nt, which are encoded by endogenous genes and are involved in the post-transcriptional regulation of gene expression in animals and plants. Studies have demonstrated that miRNAs play an important role in the occurrence, development, metastasis, diagnosis and treatment of cancer. In recent years, miR-497 has been identified as one of the key miRNAs in a variety of cancer types and has been shown to be downregulated in a variety of solid tumors. However, the regulation of miR-497 expression involves a complex network, which is affected by several factors. The aim of the present review was to summarize the mechanism of regulation of miR-497 expression at the pre-transcriptional and transcriptional levels in cancer, as well as the role of miR-497 expression imbalance in cancer diagnosis, treatment and prognosis. The regulatory mechanisms of miR-497 expression may aid in our understanding of the causes of miR-497 expression imbalance and provide a reference value for further research on the diagnosis and treatment of cancer. [ABSTRACT FROM AUTHOR]

Aberrant expression of microRNAs (miRNAs) has been associated with spinal ossification of the posterior longitudinal ligament (OPLL). Our initial bioinformatic analysis identified differentially expressed ADORA2A in OPLL and its regulatory miRNAs miR-497 and miR-195. Hence, this study was conducted to clarify the functional relevance of miR-497-195 cluster in OPLL, which may implicate in Adenosine A2A (ADORA2A). PLL tissues were collected from OPLL and non-OPLL patients, followed by quantification of miR-497, miR-195 and ADORA2A expression. The expression of miR-497, miR-195 and/or ADORA2A was altered in posterior longitudinal ligament (PLL) cells, which then were stimulated with cyclic mechanical stress (CMS). We validated that ADORA2A was expressed highly, while miR-497 and miR-195 were down-regulated in PLL tissues of OPLL patients. miR-195 and miR-497 expression in CMS-treated PLL cells was restored by a demethylation reagent 5-aza-2'-deoxycytidine (AZA). Moreover, expression of miR-195 and miR-497 was decreased by promoting promoter CpG island methylation. ADORA2A was verified as the target of miR-195 and miR-497. Overexpression of miR-195 and miR-497 diminished expression of osteogenic factors in PLL cells by inactivating the cAMP/PKA signaling pathway via down-regulation of ADORA2A. Collectively, miR-497-195 cluster augments osteogenic differentiation of PLL cells by inhibiting ADORA2A-dependent cAMP/PKA signaling pathway., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Objective: This study aimed at exploring the correlation of microRNA (miR)-497/fibroblast growth factor-23 (FGF-23) axis with major adverse cardiac and cerebral event (MACCE) occurrence in end-stage renal disease (ESRD) patients who underwent continuous ambulatory peritoneal dialysis (CAPD)., Methods: Totally, 360 ESRD patients who underwent CAPD were enrolled. Their plasma samples were collected to detect miR-497 expression by real-time quantitative polymerase chain reaction, and FGF-23 level by enzyme-linked immunosorbent assay. All patients were followed up for 36 months, and the occurrence of MACCE during the follow-up was documented., Results: MiR-497 expression negatively correlated with FGF-23 level in ESRD patients who underwent CAPD (P < .001). The MACCE occurrence rate at 1, 2, and 3-year was 5.6%, 11.9%, and 15.0%, respectively. Furthermore, miR-497/FGF-23 axis high level (P < .001) and miR-497 high expression (P = .034) correlated with reduced accumulating MACCE occurrence, whereas FGF-23 high level (P = .008) correlated with increased accumulating MACCE occurrence. Forward stepwise multivariate Cox's regression disclosed that miR-497/FGF-23 axis high level (P = .008) was an independent predictive factor for lower accumulating MACCE occurrence, whereas age (≥55 years) (P < .001), body mass index (≥21.7 kg/m 2 ) (P = .006), peritoneal dialysis duration (≥61.0 months) (P < .001), C-reactive protein (≥4.7 mg/L) (P = .001), serum uric acid (≥409.4 μmol/L) (P = .009), β-fibrinogen (≥5.8 mmol/L) (P < .001), and low-density lipoprotein cholesterol (≥2.7 mmol/L) (P = .003) were independent factors for predicting higher accumulating MACCE occurrence., Conclusion: MiR-497/FGF-23 axis holds clinical significance for predicting attenuated MACCE risk in ESRD patients who underwent CAPD., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Background: MicroRNA-497(miR-497) has been studied for its irreplaceable role of predicting the prognosis of various cancers, but there has been no systematic study to summarize the data. Consequently, we performed this meta-analysis to reveal the association between the expression level of miR-497 and cancer prognosis systematically. Materials and Methods: PubMed was searched for appropriate studies and a total of 12 eligible publications with 989 cancer patients were recruited into our analysis to assess the strength of the association. Hazard ratios (HRs) and odds ratios (ORs) were analyzed to finish this work. Results: The cancer patients who have high expressing level of miR-497 are less possible to have lymph node metastasis (OR = 0.25, 95% CI: 0.16-0.40, P < 0.001) and more likely to have favourable tumor-node-metastasis stage (OR = 0.29, 95% CI: 0.17-0.49, P < 0.001). Also, high miR-497 expression level was notably connected to better overall survival (pooled HR = 0.41, 95% CI: 0.32-0.53, P < 0.001). Conclusions: High expressing levels of miR-497 might be a potential biomarker which can be used to predict the better prognosis of different cancer types., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.