Department of Urology, The Third Affiliated Hospital of Soochow University, Jiangsu Province, China.
Biomed Pharmacother. 2016 May;80:268-275. doi: 10.1016/j.biopha.2016.03.026. Epub 2016 Apr 1.
Bladder cancer is the 7th most common cancer type in the world, and microRNAs (miRNAs) play important roles in cancer progression. In the present study, we investigated the roles and molecular mechanisms of miR-194 in bladder cancer. The results demonstrated that the expression level of miR-194 is significantly down-regulated in bladder cancer cell lines and clinical tissues. Overexpression of miR-194 inhibited cell proliferation and invasion in J82 and T24 cells. Further mechanistic study showed that overexpression of miR1-94 induced G0/G1 phase arrest as well as apoptosis in J82 and T24 cells. In addition, by using bioinformatics tool (Targetscan), RAP2B is found to be a target of miR-194, and miR-194 down-regulates the expression level of RAP2B via directly targeting its 3'UTR. Knockdown of RAP2B also inhibited cell proliferation and invasion in J28 cells. More importantly, restoration of RAP2B activity rescued the inhibitory effects of miR-194 on cell proliferation and invasion in J82 cells. Further analysis of bladder cancer clinical samples showed that miR-194 is inversely correlated with RAP2B. Collectively, our study may implicate that miR-194 plays an important role in the regulation of bladder cancer progression. In summary, our study may implicate that miR-194 acts as a tumor suppressor and plays an important role in the regulation of bladder cancer progression.
膀胱癌是世界上第 7 常见的癌症类型,microRNAs(miRNAs)在癌症进展中发挥重要作用。在本研究中,我们研究了 miR-194 在膀胱癌中的作用和分子机制。结果表明,miR-194 的表达水平在膀胱癌细胞系和临床组织中显著下调。miR-194 的过表达抑制了 J82 和 T24 细胞的增殖和侵袭。进一步的机制研究表明,miR1-94 的过表达诱导了 J82 和 T24 细胞的 G0/G1 期阻滞和凋亡。此外,通过使用生物信息学工具(Targetscan),发现 RAP2B 是 miR-194 的靶标,miR-194 通过直接靶向其 3'UTR 下调 RAP2B 的表达水平。RAP2B 的敲低也抑制了 J28 细胞的增殖和侵袭。更重要的是,RAP2B 活性的恢复挽救了 miR-194 对 J82 细胞增殖和侵袭的抑制作用。对膀胱癌临床样本的进一步分析表明,miR-194 与 RAP2B 呈负相关。总之,我们的研究表明 miR-194 在调节膀胱癌进展中发挥重要作用。综上所述,我们的研究表明 miR-194 作为一种肿瘤抑制因子,在调节膀胱癌进展中发挥重要作用。