A New Double Stranded RNA Suppresses Bladder Cancer Development by Upregulating p21 (Waf1/CIP1) Expression.
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.
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.
Chenghe
C
Wang
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.
Qiangqiang
Q
Ge
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.
Zhong
Z
Chen
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.
Jia
J
Hu
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.
Fan
F
Li
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.
Xiaodong
X
Song
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.
Hua
H
Xu
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.
Zhangqun
Z
Ye
D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019938:Cyclin D1 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000627:therapeutic use; D011401:Promoter Regions, Genetic; D012330:RNA, Double-Stranded / Q000235:genetics* / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000628:therapy
C530104:CCND1 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D035683:MicroRNAs; D012330:RNA, Double-Stranded; D019938:Cyclin D1