Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Hunan Traditional Chinese Medical College, Zhuzhou, Hunan, China.
J Biochem Mol Toxicol. 2024 Jul;38(7):e23767. doi: 10.1002/jbt.23767.
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.
微小 RNA(miRNA)是一类在癌症生物学调控中具有重要作用的小 RNA 基因。有相当多的研究关注 microRNA-505-3p(miR-505-3p)在癌症发展和进展中的作用,但 miR-505-3p 在卵巢上皮性癌(EOC)中的功能尚未完全阐明。通过比较 miRNA 表达数据集进行差异表达 miRNA 的选择。采用定量实时聚合酶链反应检测 RNA 的表达水平,采用 Western blot 和免疫荧光染色检测目的蛋白的表达水平。通过划痕愈合和 Transwell 测定评估 EOC 细胞的迁移能力。通过双荧光素酶测定研究 miRNA 和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-间充质转化显著抑制 EOC 细胞的迁移能力。此外,我们的结果表明,PEAK1 的表达被 miR-505-3p 直接结合到其 3'-UTR 抑制在 EOC 细胞中。重要的是,PEAK1 的敲低减弱了 miR-505-3p 抑制剂对 EOC 细胞迁移和侵袭的影响。总之,我们的研究结果表明,miRNA-505-3p 通过靶向 PEAK1 抑制 EOC 细胞的迁移能力。