| First Author | Nishi H | Year | 2011 |
| Journal | Mol Cell Biol | Volume | 31 |
| Issue | 4 | Pages | 744-55 |
| PubMed ID | 21149577 | Mgi Jnum | J:170404 |
| Mgi Id | MGI:4946450 | Doi | 10.1128/MCB.00581-10 |
| Citation | Nishi H, et al. (2011) MicroRNA-27a regulates beta cardiac myosin heavy chain gene expression by targeting thyroid hormone receptor beta1 in neonatal rat ventricular myocytes. Mol Cell Biol 31(4):744-55 |
| abstractText | MicroRNAs (miRNAs), small noncoding RNAs, are negative regulators of gene expression and play important roles in gene regulation in the heart. To examine the role of miRNAs in the expression of the two isoforms of the cardiac myosin heavy chain (MHC) gene, alpha- and beta-MHC, which regulate cardiac contractility, endogenous miRNAs were downregulated in neonatal rat ventricular myocytes (NRVMs) using lentivirus-mediated small interfering RNA (siRNA) against Dicer, an essential enzyme for miRNA biosynthesis, and MHC expression levels were examined. As a result, Dicer siRNA could downregulate endogenous miRNAs simultaneously and the beta-MHC gene but not alpha-MHC, which implied that specific miRNAs could upregulate the beta-MHC gene. Among 19 selected miRNAs, miR-27a was found to most strongly upregulate the beta-MHC gene but not alpha-MHC. Moreover, beta-MHC protein was downregulated by silencing of endogenous miR-27a. Through a bioinformatics screening using TargetScan, we identified thyroid hormone receptor beta1 (TRbeta1), which negatively regulates beta-MHC transcription, as a target of miR-27a. Moreover, miR-27a was demonstrated to modulate beta-MHC gene regulation via thyroid hormone signaling and to be upregulated during the differentiation of mouse embryonic stem (ES) cells or in hypertrophic hearts in association with beta-MHC gene upregulation. These findings suggested that miR-27a regulates beta-MHC gene expression by targeting TRbeta1 in cardiomyocytes. |
