Integrated analysis of MYH6, MYH7, and MYH7B expression and their associated microRNAs in human end-stage heart failure.

Authors

Zdenko Červenák, Filip Červenák, Simona Valášková, Nikola Chomaničová, Nikoleta Katreničová, Michal Hulman, Andrea Gažová, Jan Kyselovic

Published in

Frontiers in cardiovascular medicine. Volume 13. Pages 1879458. Epub Aug 07, 2026.

Abstract

Cardiac contractility is regulated by two myosin heavy chain (MHC) protein isoforms, α and β, encoded by the MYH6 and MYH7 genes. The intronic regions of these genes encode the microRNAs miR-208a and miR-208b, which are key regulators of cardiac hypertrophy. Functionally relevant long non-coding RNAs (lncRNAs) have also been identified at these loci, such as those transcribed in the antisense direction from the MYH7 gene, including the primary miR-208b transcript (MHRT) originating from an internal MYH7 promoter. Additionally, MYH7B, another cardiac sarcomeric myosin gene, serves as a precursor for miR-499a-5p.
This study aimed to comprehensively analyse the expression profiles of MYH6, MYH7, and MYH7B genes, microRNAs (miR-208a-3p, miR-208b-3p, and miR-499a-5p), and the lncRNA MHRT in non-failing and end-stage failing human left ventricles.
The relative expression of these transcripts was measured using RT-qPCR in left ventricular samples from 5 non-failing controls and 24 patients with end-stage heart failure, including hypertrophic cardiomyopathy (HCM, n = 4), dilated cardiomyopathy (DCM, n = 10), and coronary artery disease (CAD, n = 10). The findings were validated by comparison with two independent RNA-seq datasets (GSE141910 and GSE116250) for MYH6, MYH7, MYH7B, and MHRT.
Statistical analysis of independent RNA-seq datasets confirmed strong correlations among MYH7, MYH7B, and MHRT transcripts (p ≤ 0.0001), a trend also observed in our RT-qPCR cohort. A profound imbalance in the MYH7B/miR-499-5p ratio was identified, shifting from ∼250:1 in non-failing controls to ∼12-18:1 in failing hearts. The miR-208a-3p/miR-208b-3p expression ratio was heavily skewed toward miR-208b-3p (∼50:1) in all groups, regardless of disease status.
Our results suggest that MYH7, MYH7B, and MHRT transcripts exhibit coordinated expression patterns in human left ventricles, independent of pathological status. We further observed a dissociation between miR-208a-3p and its host gene (MYH6) under physiological conditions and confirmed altered miR-499a-5p/MYH7B relationships, consistent with findings in murine models. Moreover, the expression of two regulatory genes, SOX6 and TARBP2, known to modulate MYH7 and MYH7B in mice, showed that SOX6 is upregulated in the left ventricles of all pathological groups.

PMID:
42630156
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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