Key result
Bioinformatics links m6A-related regulators to HCM, highlighting a crucial immune system role.
Why the study?
Hypertrophic cardiomyopathy is the most common inherited heart disease, but the correlation between m6A RNA modification and immune infiltrates remained to be constructed.
Bioinformatics analysis and preclinical validation identified key m6A RNA modification-related genes and immune infiltrates that may play a crucial role in the pathogenesis of hypertrophic cardiomyopathy.
Answers are grounded in this paper and cite their sources.
Should not yet change hypertrophic cardiomyopathy practice; hypothesis-generating for m6A and immune roles.
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. We performed a comprehensive analysis to construct the correlation of m6A and immune in HCM. Two HCM datasets (GSE141910 and GSE160997) and m6A-related regulators were obtained from GEO and published articles, respectively. Differentially expressed m6A-related regulators were obtained. Random forest model and nomogram were conducted to assess the risk of HCM, and finally, the m6A subtype was constructed. Functional enrichment analysis was conducted. Protein-protein interaction network of differentially expressed genes between m6A subtypes was performed. Furthermore, we constructed the Hubgene-chemical network, Hubgene-microRNA network, and Hubgene-transcription factor network of the top 10 hubgenes. Additionally, the immune subtype and hubgene subtype were constructed. PCR was performed to validate the m6A-related regulators. We obtained 20 m6A-related regulators in HCM. Among them, 8 m6A-related regulators differentially expressed (YTHDC1, HNRNPC, and FMR1 were up-regulated while YTHDC2, FTO, WTAP, IGF2BP2, and IGF2BP3 were down-regulated). FTO, FMR1, IGF2BP3, YTHDC1, and IGF2BP2 were the top 5 important m6A-related regulators and were used to conduct the nomogram. We obtained 329 differentially expressed genes in m6A subtype and these genes enriched HCM-related processes and pathways. Furthermore, we constructed the Hubgene-chemical network, Hubgene-microRNA network, and Hubgene-transcription factor network of the top 10 hubgenes (NFKBIA, NFKB1, PSMA3, PSMC4, PSMA2, PSMA4, PSMD7, PSMD10, PSMD8, and PSMA6). And then we constructed an immune subtype based on the immune cell infiltration levels and hubgene subtype based on the expression of the top 10 hubgenes. Finally, we verified the main results through experiments. In conclusion, we built a nomogram and identified 8 m6A-related regulators and 10 hubgenes, which were prominently associated with HCM. We found that m6A and the immune system may play a crucial role in the HCM. Accordingly, those genes and pathways might become therapeutic targets with clinical usefulness in the future.
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Hu et al. (2024) studied Hypertrophic cardiomyopathy. Bioinformatics analysis identified 8 m6A-related regulators and 10 hubgenes prominently associated with hypertrophic cardiomyopathy, suggesting m6A and the immune system play a crucial role in the disease.
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