miR-29a activates expression of α-cardiac myosin heavy chain via β1 thyroid hormone receptor in neonatal rats

Arch Med Sci. 2020 Jan 8;20(2):641-654. doi: 10.5114/aoms.2019.91495. eCollection 2024.

Abstract

Introduction: MicroRNAs (miRs) are small noncoding RNAs which are regulators of gene expression and also regulate the genes in heart tissues. The aim of the study was to evaluate the effect of miRs on the expression level of myosin heavy chain (MHC), which is responsible for regulation of cardiac functions in neonatal rat ventricular myocytes and mice.

Material and methods: The miRs were suppressed in neonatal rat ventricular myocytes using small interfering RNAs (siRNAs) against Dicer followed by evaluation of MHC levels. For in vivo study the C57 black/6 Jacksonian mice were subjected to the transverse aortic constriction (TAC) procedure.

Results: The Dicer siRNA suppressed the endogenous miRs and the α-MHC gene but failed to down-regulate the β-MHC. Among the 17 selected miRs, miR-29a was found to up-regulate the α-MHC gene significantly but not β-MHC. The expression of α-MHC was suppressed by silencing the expression of miR-29a. Bioinformatics study done by TargetScan suggested thyroid hormone receptor-β1 (TR-β1) as a potential target of miR-29a. Additionally, miR-29a was found to regulate the expression of α-MHC via TR-β1 signaling.

Conclusions: The findings of the present study indicated that miR-29a modulates expression of α-the MHC gene by targeting TR-β1 in cardiac cells. The study may provide a new direction for treating cardiac failure and cardiac hypertrophy.

Keywords: cardiac cells; miR-29a; thyroid hormone receptor-β1; α-myosin heavy chain.