Open Access

miR‑449a‑5p suppresses CDK6 expression to inhibit cardiomyocyte proliferation

  • Authors:
    • Bing Li
    • Zhi Wang
    • Fan Yang
    • Jing Huang
    • Xingwei Hu
    • Shiyan Deng
    • Maobo Tian
    • Xiaoyun Si
  • View Affiliations

  • Published online on: November 3, 2020     https://doi.org/10.3892/mmr.2020.11652
  • Article Number: 14
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Induction of cardiomyocyte (CM) proliferation is a promising approach for cardiac regeneration following myocardial injury. MicroRNAs (miRs) have been reported to regulate CM proliferation. In particular, miR‑449a‑5p has been identified to be associated with CM proliferation in previous high throughput functional screening data. However, whether miR‑449a‑5p regulates CM proliferation has not been thoroughly investigated. This study aimed to explore whether miR‑449a‑5p modulates CM proliferation and to identify the molecular mechanism via which miR‑449a‑5p regulates CM proliferation. The current study demonstrated that miR‑449a‑5p expression levels were significantly increased during heart development. Furthermore, the results suggested that miR‑449a‑5p mimic inhibited CM proliferation in vitro as determined via immunofluorescence for ki67 and histone H3 phosphorylated at serine 10 (pH3), as well as the numbers of CMs. However, miR‑449a‑5p knockdown promoted CM proliferation. CDK6 was identified as a direct target gene of miR‑449a‑5p, and CDK6 mRNA and protein expression was suppressed by miR‑449a‑5p. Moreover, CDK6 gain‑of‑function increased CM proliferation. Overexpression of CDK6 also blocked the inhibitory effect of miR‑449a‑5p on CM proliferation, indicating that CDK6 was a functional target of miR‑449a‑5p in CM proliferation. In conclusion, miR‑449a‑5p inhibited CM proliferation by targeting CDK6, which provides a potential molecular target for preventing myocardial injury.
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January-2021
Volume 23 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Li B, Wang Z, Yang F, Huang J, Hu X, Deng S, Tian M and Si X: miR‑449a‑5p suppresses CDK6 expression to inhibit cardiomyocyte proliferation. Mol Med Rep 23: 14, 2021
APA
Li, B., Wang, Z., Yang, F., Huang, J., Hu, X., Deng, S. ... Si, X. (2021). miR‑449a‑5p suppresses CDK6 expression to inhibit cardiomyocyte proliferation. Molecular Medicine Reports, 23, 14. https://doi.org/10.3892/mmr.2020.11652
MLA
Li, B., Wang, Z., Yang, F., Huang, J., Hu, X., Deng, S., Tian, M., Si, X."miR‑449a‑5p suppresses CDK6 expression to inhibit cardiomyocyte proliferation". Molecular Medicine Reports 23.1 (2021): 14.
Chicago
Li, B., Wang, Z., Yang, F., Huang, J., Hu, X., Deng, S., Tian, M., Si, X."miR‑449a‑5p suppresses CDK6 expression to inhibit cardiomyocyte proliferation". Molecular Medicine Reports 23, no. 1 (2021): 14. https://doi.org/10.3892/mmr.2020.11652