title: CDK6 mediates the effect of attenuation of miR-1 on provoking cardiomyocyte hypertrophy.
abstract: MicroRNA-1 (miR-1) is approved involved in cardiac hypertrophy, but the underlying molecular mechanisms of miR-1 in cardiac hypertrophy are not well elucidated. The present study aimed to investigate the potential role of miR-1 in modulating CDKs-Rb pathway during cardiomyocyte hypertrophy. A rat model of hypertrophy was established with abdominal aortic constriction, and a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocytes (NRVCs). We demonstrated that miR-1 expression was markedly decreased in hypertrophic myocardium and hypertrophic cardiomyocytes. Dual luciferase reporter assays revealed that miR-1 interacted with the 3'UTR of CDK6, and miR-1 was verified to inhibit CDK6 expression at the posttranscriptional level. CDK6 protein expression was observed increased in hypertrophic myocardium and hypertrophic cardiomyocytes. Morover, miR-1 mimic, in parallel to CDK6 siRNA, could inhibit PE-induced hypertrophy of NRVCs, with decreases in cell size, newly transcribed RNA, expressions of ANF and β-MHC, and the phosphorylated pRb. Taken together, our results reveal that derepression of CDK6 and activation of Rb pathway contributes to the effect of attenuation of miR-1 on provoking cardiomyocyte hypertrophy.
authors.affiliation: Medical Research Department of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Tang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China.
authors.forename: Wensi
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Medical Research Department of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Jiening
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Medical Research Department of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Qiuxiong
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Medical Research Department of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Yongheng
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Medical Research Department of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Deng
authors.affiliation: Medical Research Department of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Medical Research Department of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Medical Research Department of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Shulin
authors.initials: S
authors.lastname: Wu
authors.affiliation: Medical Research Department of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People's Republic of China. zhixinshan@aliyun.com.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Shan
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C542191:MIRN1 microRNA, rat; D035683:MicroRNAs; D034741:RNA, Small Interfering; C495913:Cdk6 protein, rat; D051361:Cyclin-Dependent Kinase 6
keywords: CDK6; Cardiac hypertrophy; Cardiomyocyte; MicroRNA-1