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CDK6 mediates the effect of attenuation of miR-1 on provoking cardiomyocyte hypertrophy

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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.

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Acknowledgments

This work was supported by Grants from The National Natural Science Foundation of China (81470439, 81270222, 81070102) and by Grants from Guangdong Province (No. 2014A030313635, S2012010009453, S2011020005911, 1563000369, and A2015187).

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Authors and Affiliations

  1. Medical Research Department of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People’s Republic of China

    Weiwei Yuan, Jiening Zhu, Qiuxiong Lin, Yongheng Fu, Chunyu Deng, Yumei Xue, Min Yang, Shulin Wu & Zhixin Shan

  2. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China

    Chunmei Tang & Wensi Zhu

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  1. Weiwei Yuan
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  2. Chunmei Tang
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  3. Wensi Zhu
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  4. Jiening Zhu
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  5. Qiuxiong Lin
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  11. Zhixin Shan
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Correspondence to Zhixin Shan.

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Wei-wei Yuan and Chun-mei Tang are joint first authors.

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Yuan, W., Tang, C., Zhu, W. et al. CDK6 mediates the effect of attenuation of miR-1 on provoking cardiomyocyte hypertrophy. Mol Cell Biochem 412, 289–296 (2016). https://doi.org/10.1007/s11010-015-2635-4

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  • DOI: https://doi.org/10.1007/s11010-015-2635-4

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