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, α- and β-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 β-MHC gene but not α-MHC, which implied that specific 
miRNAs could upregulate the β-MHC gene. Among 19 selected miRNAs, miR-27a was 
found to most strongly upregulate the β-MHC gene but not α-MHC. Moreover, β-MHC 
protein was downregulated by silencing of endogenous miR-27a. Through a 
bioinformatics screening using TargetScan, we identified thyroid hormone 
receptor β1 (TRβ1), which negatively regulates β-MHC transcription, as a target 
of miR-27a. Moreover, miR-27a was demonstrated to modulate β-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 
β-MHC gene upregulation. These findings suggested that miR-27a regulates β-MHC 
gene expression by targeting TRβ1 in cardiomyocytes.