First Author | Li B | Year | 2021 |
Journal | Mol Med Rep | Volume | 23 |
Issue | 1 | PubMed ID | 33179102 |
Mgi Jnum | J:305376 | Mgi Id | MGI:6706232 |
Doi | 10.3892/mmr.2020.11652 | Citation | Li B, et al. (2021) miR449a5p suppresses CDK6 expression to inhibit cardiomyocyte proliferation. Mol Med Rep 23(1) |
abstractText | 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, miR449a5p has been identified to be associated with CM proliferation in previous high throughput functional screening data. However, whether miR449a5p regulates CM proliferation has not been thoroughly investigated. This study aimed to explore whether miR449a5p modulates CM proliferation and to identify the molecular mechanism via which miR449a5p regulates CM proliferation. The current study demonstrated that miR449a5p expression levels were significantly increased during heart development. Furthermore, the results suggested that miR449a5p mimic inhibited CM proliferation <em>in vitro</em> as determined via immunofluorescence for ki67 and histone H3 phosphorylated at serine 10 (pH3), as well as the numbers of CMs. However, miR449a5p knockdown promoted CM proliferation. CDK6 was identified as a direct target gene of miR449a5p, and CDK6 mRNA and protein expression was suppressed by miR449a5p. Moreover, CDK6 gainoffunction increased CM proliferation. Overexpression of CDK6 also blocked the inhibitory effect of miR449a5p on CM proliferation, indicating that CDK6 was a functional target of miR449a5p in CM proliferation. In conclusion, miR449a5p inhibited CM proliferation by targeting CDK6, which provides a potential molecular target for preventing myocardial injury. |