The suppressive effects of miR-1180-5p on the proliferation and tumorigenicity of bladder cancer cells.
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.
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Qiangqiang
Q
Ge
Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Chenghe
C
Wang
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. chenzhongtongji@126.com.
Zhong
Z
Chen
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Fan
F
Li
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Jia
J
Hu
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Zhangqun
Z
Ye
D000818:Animals; D015153:Blotting, Western; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C000613368:MIRN1180 microRNA, human; D035683:MicroRNAs