title: MiR-124 retards bladder cancer growth by directly targeting CDK4.
abstract: MicroRNAs (miRNAs) are a class of non-coding small RNAs that act as negative regulators of gene expression by binding to the 3'-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-dependent kinase (CDK4), which has been implicated as a regulator of cell cycle, was chosen for further study. MiR-124 could significantly repress CDK4 expression by targeting its binding site in the 3'UTR of CDK4 in vitro. In both bladder cancer cell lines and tissues, the expression of miR-124 was significantly down-regulated, while CDK4 expression was up-regulated. Ectopic expression of miR-124 in transplanted HT1197 cells resulted in the retardation of tumor growth in mouse tumor xenografts. And the expression of miR-124 and CDK4 showed an obvious inverse correlation 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.
authors.affiliation: Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin 300211, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin 300211, China Department of Gynaecology, Second Hospital of Tianjin Medical University, Tianjin 300211, China Department of Gynaecology and Obstetrics, Tangshan Maternal and Children Health Hospital, Tangshan 063000, China.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Changhai Hospital affiliated to Second Military Medical University, Shanghai 200433, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhai
authors.affiliation: Institute of Basic Medicine, Hebei United University, Tangshan 063000, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Li
authors.affiliation: Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin 300211, China.
authors.forename: Changying
authors.initials: C
authors.lastname: Li
authors.affiliation: Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin 300211, China jiwu_chang@163.com.
authors.forename: Jiwu
authors.initials: J
authors.lastname: Chang
mesh_terms: D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division / Q000502:physiology*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000473:pathology*
chemical_list: D017931:DNA Primers; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051358:Cyclin-Dependent Kinase 4
keywords: CDK4; bladder cancer; miR-124