Wang Chenghe, Ge Qiangqiang, Chen Zhong, Hu Jia, Li Fan, Song Xiaodong, Xu Hua, Ye Zhangqun
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Wuhan, Hubei 430030, China ; Institute of Urology of Hubei Province, No. 1095 Jie Fang Avenue, Wuhan, Hubei 430030, China.
Biomed Res Int. 2015;2015:304753. doi: 10.1155/2015/304753. Epub 2015 Mar 30.
We have previously demonstrated that miR-1180-5p has potent ability to upregulate p21 expression by targeting promoter and inhibit bladder cancer. This prompted us to conjecture that a candidate dsRNA (dsP21-397) with perfect complementarity to the miR-1180-5p target site of p21 promoter may also trigger p21 expression. Transfection of dsP21-397 into T24 and EJ cells significantly activated p21 expression at 72 h and the activation presented in a time-course and dose-dependent manner. Moreover, the p21-activated activities of dsP21-397 and miR-1180-5p are not significantly different. Overexpression of p21 downregulated Cyclin D1, CDK4/6, and Cyclin A2 expression, and thereby induced cell cycle arrest and inhibited proliferation. Moreover, dsP21-397 suppressed bladder cancer largely depended on manipulating p21. In conclusion, our study identifies a pair of miRNA-dsRNA mediating endogenous p21 overexpression.
我们之前已经证明,miR-1180-5p具有通过靶向启动子上调p21表达并抑制膀胱癌的强大能力。这促使我们推测,一种与p21启动子的miR-1180-5p靶位点具有完美互补性的候选双链RNA(dsP21-397)也可能触发p21表达。将dsP21-397转染到T24和EJ细胞中,在72小时时显著激活了p21表达,且这种激活呈现出时间进程和剂量依赖性。此外,dsP21-397和miR-1180-5p对p21的激活活性没有显著差异。p21的过表达下调了细胞周期蛋白D1、细胞周期蛋白依赖性激酶4/6和细胞周期蛋白A2的表达,从而诱导细胞周期停滞并抑制增殖。此外,dsP21-397对膀胱癌的抑制很大程度上依赖于对p21的调控。总之,我们的研究鉴定出了一对介导内源性p21过表达的miRNA-双链RNA。