关键词: PEAK1 epithelial ovarian cancer invasion miRNA‐505‐3p migration

Mesh : MicroRNAs / genetics metabolism Humans Cell Movement Female Ovarian Neoplasms / genetics pathology metabolism Carcinoma, Ovarian Epithelial / genetics metabolism pathology Cell Line, Tumor Gene Expression Regulation, Neoplastic Epithelial-Mesenchymal Transition / genetics

来  源:   DOI:10.1002/jbt.23767

Abstract:
MicroRNAs (miRNAs) are a class of small RNA genes with important roles in cancer biology regulation. There are considerable studies regarding the roles of microRNA-505-3p (miR-505-3p) in cancer development and progression, but the function of miR-505-3p in epithelial ovarian cancer (EOC) has not been fully clarified. Comparative analysis of miRNA expression data set was used to select differentially expressed miRNAs. Quantitative real-time polymerase chain reaction was applied to detect expression levels of RNAs, while western blot and immunofluorescence staining were performed to detect expression levels of proteins of interest. The motility of EOC cells was assessed by wound healing and transwell assays. The binding and regulating relationship between miRNA and its direct target gene was investigated by dual-luciferase assay. Our results show that miR-505-3p was upregulated in recurrent EOC, which significantly inhibits EOC cell motility via modulating cell epithelial-mesenchymal transition. Furthermore, our results indicated that PEAK1 expression was inhibited by direct binding of miR-505-3p into its 3\'-URT in EOC cells. Importantly, knockdown of PEAK1 attenuated the effect of mi-505-3p inhibitor on EOC cell migration and invasion. In conclusion, our findings indicate that miRNA-505-3p inhibits EOC cell motility by targeting PEAK1.
摘要:
MicroRNAs(miRNAs)是一类在肿瘤生物学调控中具有重要作用的小RNA基因。关于microRNA-505-3p(miR-505-3p)在癌症发展和进展中的作用,有相当多的研究。但miR-505-3p在上皮性卵巢癌(EOC)中的功能尚未完全阐明。miRNA表达数据集的比较分析用于选择差异表达的miRNA。定量实时聚合酶链反应用于检测RNA的表达水平,同时进行蛋白质印迹和免疫荧光染色以检测目的蛋白的表达水平。通过伤口愈合和transwell测定来评估EOC细胞的运动性。通过双荧光素酶实验研究了miRNA与其直接靶基因之间的结合和调节关系。我们的结果表明,miR-505-3p在复发性EOC中上调,通过调节细胞上皮-间质转化显著抑制EOC细胞运动。此外,我们的结果表明,在EOC细胞中,通过将miR-505-3p直接结合到其3'-URT中来抑制PEAK1的表达.重要的是,敲除PEAK1减弱mi-505-3p抑制剂对EOC细胞迁移和侵袭的影响。总之,我们的发现表明miRNA-505-3p通过靶向PEAK1抑制EOC细胞运动.
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