title: CDK3 is a major target of miR-150 in cell proliferation and anti-cancer effect.
abstract: MiR-150, a member of small non-coding RNAs, has been proven to dysregulate in different types of tumor and bear on carcinogenesis and cancer prognosis by regulating the expression of a series of gene including utrophin. Given that utrophin can compensate for dystrophin's absence and be regarded as a promising therapeutic target for Duchenne Muscular Dystrophy (DMD), we further detected the deep role of miR-150 in dystrophic muscle. Using a range of bioinformatic, molecular and cell biology techniques, we declared that miR-150 directly targets cyclin-dependent kinase 3 (CDK3) and leads to the regulation of CDK3 gene expression in both muscle-derived and non-muscle cells. The results indicated the expression of miR-150 was upregulated in mdx muscle and closely related to the lower level of CDK3. Transient transfection of miR-150 into cultured C2C12 cells led to significant decrease in cell proliferation, which is partly mediated via the 3'-UTRs of CDK3 mRNA. Targeting of CDK3 could also play a role, at least in part, in the anti-cancer activity suggested for miR-150 in previous studies. Consistently, the analysis of tumor and matched normal lung tissues indicates that miR-150 downregulation in lung tumors correlates with higher CDK3 levels. In addition, miR-150 transfection experiments with cancer-derived cell lines reveal that miR-150-mediated CDK3 suppression directly induces to growth inhibition. Collectively, our results highlight a novel activity for CDK3 in myoblast cell proliferation and confirm CDK3 as a key target that further enhances the tumor suppressor function proposed for miR-150.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, China.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, China.
authors.forename: Chengcao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, China.
authors.forename: Qiqiang
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, China. Electronic address: djli@whu.edu.cn.
authors.forename: Dejia
authors.initials: D
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056849:Cyclin-Dependent Kinase 3 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D056849:Cyclin-Dependent Kinase 3; D035683:MicroRNAs; C533097:MIR150, human; C098776:CDK3 protein, human
keywords: CDK3; Cell proliferation; Tumor suppressor; miR-150