Lu Shu, Wang Ming-Shan, Chen Pei-Jie, Ren Qiang, Bai Peiming
Department of Urology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China.
Exp Ther Med. 2017 Jun;13(6):3309-3314. doi: 10.3892/etm.2017.4387. Epub 2017 Apr 26.
microRNAs (miRNAs) are known to be important in tumor initiation and progression. Recent studies have demonstrated that miR-186 is critical in several types of cancer, including human non-small cell lung cancer, bladder cancer and pancreatic ductal adenocarcinoma. However, the functions of miR-186 in prostate cancer (PCa) are still unclear. In the present study, downregulation of miR-186 in PCa cells was detected when compared with the normal prostate cell line. When miR-186 overexpressed in PCa cells, cell proliferation was evidently inhibited as shown using cell counting kit-8 assays and cell-cycle analysis, and tumor growth was decreased as shown by tumor growth assays in nude mice. Furthermore, through bioinformatics prediction and biochemical analyses, Yin Yang 1 (YY1) and cyclin-dependent kinase 6 (CDK6) have been proven to act as direct targets of miR-186. These results indicate that miR-186 is a negative regulator in PCa by inhibiting PCa cell proliferation via targeting YY1 and CDK6.
微小RNA(miRNA)在肿瘤的发生和发展过程中发挥着重要作用。近期研究表明,miR-186在包括人类非小细胞肺癌、膀胱癌和胰腺导管腺癌在内的多种癌症中起着关键作用。然而,miR-186在前列腺癌(PCa)中的功能仍不明确。在本研究中,与正常前列腺细胞系相比,PCa细胞中miR-186表达下调。当PCa细胞中miR-186过表达时,使用细胞计数试剂盒-8检测和细胞周期分析表明细胞增殖明显受到抑制,裸鼠肿瘤生长实验显示肿瘤生长减缓。此外,通过生物信息学预测和生化分析,已证实阴阳1(YY1)和细胞周期蛋白依赖性激酶6(CDK6)是miR-186的直接靶点。这些结果表明,miR-186通过靶向YY1和CDK6抑制PCa细胞增殖,是PCa中的一种负调控因子。