Ge Qiangqiang, Wang Chenghe, Chen Zhong, Li Fan, Hu Jia, Ye Zhangqun
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Histol Histopathol. 2017 Jan;32(1):77-86. doi: 10.14670/HH-11-772. Epub 2016 Apr 26.
In our previous research, we have reported that a candidate microRNA (miR-1180-5p) has the capacity to induce overexpression of tumor suppressor gene p21 and inhibit the growth of human bladder cancer (BCa) cell lines in vitro. However, the exact mechanism as to how miR-1180-5p suppresses BCa cell proliferation remains unknown, and the inhibitory effect of miR-1180-5p in vivo also need to be investigated. In the present study, we found that the expression level of miR-1180-5p was lower in BCa cells than in normal human urothelial cells. Furthermore, we found that overexpression of p21, activated by miR-1180-5p, interfered with cell cycle progress by inhibiting the cell cycle related proteins (CDK4, CDK6, Cyclin D1 and Cyclin A2), and thereby suppressed BCa cell proliferation. In addition, miR-1180-5p also suppressed the tumor growth in vivo significantly. Taken together, our study provides evidence that up-regulation of p21 is mainly responsible for the suppressive effect of miR-1180-5p on BCa cells and miR-1180-5p can significantly inhibit tumorigenicity in vivo.
在我们之前的研究中,我们报道了一种候选微小RNA(miR-1180-5p)能够诱导肿瘤抑制基因p21的过表达,并在体外抑制人膀胱癌细胞系的生长。然而,miR-1180-5p抑制膀胱癌细胞增殖的确切机制仍不清楚,其在体内的抑制作用也有待研究。在本研究中,我们发现miR-1180-5p在膀胱癌细胞中的表达水平低于正常人尿路上皮细胞。此外,我们发现由miR-1180-5p激活的p21过表达通过抑制细胞周期相关蛋白(CDK4、CDK6、细胞周期蛋白D1和细胞周期蛋白A2)干扰细胞周期进程,从而抑制膀胱癌细胞增殖。此外,miR-1180-5p在体内也显著抑制肿瘤生长。综上所述,我们的研究提供了证据,表明p21的上调主要负责miR-1180-5p对膀胱癌细胞的抑制作用,并且miR-1180-5p在体内可显著抑制肿瘤发生。