Key result
Patients with familial hypertrophic cardiomyopathy carrying MYBPC3 gene mutations exhibited 33 significantly differentially expressed miRNAs, with miR-208b-3p being significantly upregulated compared to healthy controls.
Why the study?
MicroRNAs play an important role in familial hypertrophic cardiomyopathy pathogenesis, but the miRNA profile in patients with MYBPC3 gene mutations was not established.
Case-Control (n=6)
No
FHCM patients with MYBPC3 mutations exhibit a specific miRNA expression profile, notably the upregulation of miR-208b-3p, which may promote cardiac hypertrophy via the Wnt signaling pathway.
Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in the pathogenesis of FHCM. In the present study, we aimed to determine the miRNA profile in FHCM patients with myosin-binding protein C3 (MYBPC3) gene mutations. We recruited three FHCM patients and age- and sex-matched controls. The three probands all had hypertrophic obstructive cardiomyopathy with severe myocardial hypertrophy, and two of the three had a history of sudden cardiac death, representing a "malignant" phenotype. We then compared the miRNA expression profiles of three FHCM patients carrying MYBPC3 gene mutations with those of the normal control group using miRNA sequencing technology. Differentially expressed miRNAs were verified using real-time polymerase chain reaction (qPCR). Target genes and signaling pathways of the identified differentially expressed miRNAs were predicted using bioinformatics analysis. A total of 33 significantly differentially expressed miRNAs were detected in the peripheral blood of the three probands, of which 28 were upregulated, including miR-208b-3p, and 5 were downregulated. Real-time PCR confirmed the upregulated expression of miR-208b-3p in FHCM patients (P < 0.05). Bioinformatics analysis showed that miR-208b-3p was mainly enriched in 79 target genes including UBE2V2, MED13, YBX1, CNKSR2, GATA4, andSOX5/6, et al. Gene ontology (GO) analysis of target genes showed that miR-208b was mainly involved in the processes of negative regulation of transcription from RNA polymerase II promoter, and regulation of transcription, DNA templated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target genes regulated by miR-208b-3p were mainly involved in the Wnt signaling pathway. These findings suggest that FHCM patients with MYBPC3 gene mutations have a specific miRNA expression profile, and that miR-208b-3p is significantly upregulated in cardiac hypertrophy. Our results also indicate that miRNA-208b-3p activates the Wnt signaling pathway through its target gene to promote cardiac hypertrophy.
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Lin et al. (2022) conducted a case-control in Familial hypertrophic cardiomyopathy with MYBPC3 gene mutations (n=6). MYBPC3 gene mutation (FHCM) vs. Healthy controls was evaluated on Differentially expressed miRNAs in peripheral blood (p=<0.05). Patients with familial hypertrophic cardiomyopathy carrying MYBPC3 gene mutations exhibited 33 significantly differentially expressed miRNAs, with miR-208b-3p being significantly upregulated compared to healthy controls.
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