MiR-124 retards bladder cancer growth by directly targeting CDK4  

作　　者：Ting Zhang Jingyao Wang Xiaofeng Zhai Hongjie Changying Li Jiwu Chang 

机构地区：[1]Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin 300211, China [2]Department of Gynaecology, Second Hospital of Tianjin Medical University, Tianjin 300211, China [3]Department of Gynaecology and Obstetrics, Tangshan Maternal and Children Health Hospital, Tangshan 063000, China [4]Department of Traditional Chinese Medicine, Changhai Hospital affiliated to Second Military Medical University, Shanghai 200433, China [5]Institute of Basic Medicine, Hebei United University, Tangshan 063000, China

出　　处：《Acta Biochimica et Biophysica Sinica》2014年第12期1072-1079,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the Tianjin Natural Science Foundation （13JCQNJCll500; to C.L.）, the Specialized Research Fund for Doctoral Program of Higher Education （SRFDP） （20121202120003; to C.L.）, the Science and Technology Foundation of Tianjin Public Health Bureau of China （2013KZ113; to T.Z.）, and the Tianjin City High School Science ＆ Technology Fund Planning Project （20120133 to Ci.）.

摘　　要：MicroRNAs （miRNAs） are a class of non-coding small RNAs that act as negative regulators of gene expression by binding to the 31-untranslated region （3＇UTR） of target mRNAs. In order to investigate the physiological role of miR-124 in bladder cancer, target genes of miR-124 were predicted by the TargetScan software, and cyclin-depend- ent kinase （CDK4）, which has been implicated as a regula- tor of cell cycle, was chosen for further study. MiR-124 could significantly repress CDK4 expression by targeting its binding site in the 31UTR of CDK4 in vitro. In both bladder cancer cell lines and tissues, the expression of miR- 124 was significantly down-regulated, while CDK4 expres- sion was up-regulated. Ectopic expression of miR-124 in transplanted HTl197 cells resulted in the retardation of tumor growth in mouse tumor xenografts. And the expres- sion of miR-124 and CDK4 showed an obvious inverse cor- relation in these xenograft tissues, which was also observed in human bladder cancer tissue samples. Taken together, our results strongly suggest that miR-124 can arrest cell cycle and restrain the growth of bladder cancer by targeting CDK4 directly.MicroRNAs （miRNAs） are a class of non-coding small RNAs that act as negative regulators of gene expression by binding to the 31-untranslated region （3＇UTR） of target mRNAs. In order to investigate the physiological role of miR-124 in bladder cancer, target genes of miR-124 were predicted by the TargetScan software, and cyclin-depend- ent kinase （CDK4）, which has been implicated as a regula- tor of cell cycle, was chosen for further study. MiR-124 could significantly repress CDK4 expression by targeting its binding site in the 31UTR of CDK4 in vitro. In both bladder cancer cell lines and tissues, the expression of miR- 124 was significantly down-regulated, while CDK4 expres- sion was up-regulated. Ectopic expression of miR-124 in transplanted HTl197 cells resulted in the retardation of tumor growth in mouse tumor xenografts. And the expres- sion of miR-124 and CDK4 showed an obvious inverse cor- relation in these xenograft tissues, which was also observed in human bladder cancer tissue samples. Taken together, our results strongly suggest that miR-124 can arrest cell cycle and restrain the growth of bladder cancer by targeting CDK4 directly.

关 键 词：miR-124 bladder cancer CDK4 

分 类 号：Q26[生物学—细胞生物学] TQ658.34[化学工程—精细化工]