Department of gerontology, Yantaishan Hospital, Yantai, Shandong, China.
Biotechnol Genet Eng Rev. 2024 Oct;40(2):961-975. doi: 10.1080/02648725.2023.2191086. Epub 2023 Mar 21.
We explored -methyladenosine (m6A) RNA methylation as one of the gene regulatory mechanisms in heart failure (HF) biology. Understanding the different physiological mechanisms will facilitate the prevention and individualized treatment of HF. The Gene Expression Omnibus (GEO) database served as the source of the data. In GSE116250, differential analysis between ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM) and controls yielded differentially expressed m6A regulators. Differential analysis between HF and controls in GSE131296 identifies m6A-modified genes and then performs enrichment analysis. Protein-protein interaction (PPI) network analysis was performed for the differentially expressed ICM- or DCM-associated genes in GSE116250 and GSE55296, respectively. Finally, the diagnostic genes for ICM and DCM were predicted using receiver operating characteristic (ROC) curve. YTHDC1, HNRNPC and HNRNPA2B1 were significantly downregulated in GSE116250 in DCM and ICM compared with controls. A total of 195 genes were identified in GSE131296 as subject to m6A alteration. These genes may play a role in HF through the MAPK signaling pathway and p53 signaling pathway. PPI network analysis identified , and as key genes for ICM and as a key gene for DCM. Through ROC curves, we identified m6A-modified , as potential diagnostic genes for ICM, and m6A-modified , and as potential diagnostic genes for DCM. Our findings support m6A modifying mechanisms in HF etiology that contribute to the treatment of HF. Thus, our data suggest that m6A methylation may be an interesting target for therapeutic intervention.
我们探索了 - 甲基腺苷（m6A）RNA 甲基化作为心力衰竭（HF）生物学中基因调控机制之一。了解不同的生理机制将有助于 HF 的预防和个体化治疗。基因表达综合数据库（GEO）是数据的来源。在 GSE116250 中，缺血性心肌病（ICM）、扩张型心肌病（DCM）和对照组之间的差异分析产生了差异表达的 m6A 调节剂。GSE131296 中 HF 和对照组之间的差异分析确定了 m6A 修饰基因，然后进行了富集分析。分别对 GSE116250 和 GSE55296 中差异表达的 ICM 或 DCM 相关基因进行蛋白质-蛋白质相互作用（PPI）网络分析。最后，使用受试者工作特征（ROC）曲线预测了 ICM 和 DCM 的诊断基因。在 GSE116250 中，与对照组相比，DCM 和 ICM 中 YTHDC1、HNRNPC 和 HNRNPA2B1 显著下调。在 GSE131296 中，共有 195 个基因被鉴定为 m6A 改变。这些基因可能通过 MAPK 信号通路和 p53 信号通路在 HF 中发挥作用。PPI 网络分析确定 、 和 是 ICM 的关键基因， 是 DCM 的关键基因。通过 ROC 曲线，我们确定了 m6A 修饰的 、 和 是 ICM 的潜在诊断基因，而 m6A 修饰的 、 和 是 DCM 的潜在诊断基因。我们的研究结果支持 HF 病因中的 m6A 修饰机制，有助于 HF 的治疗。因此，我们的数据表明 m6A 甲基化可能是治疗干预的一个有趣靶点。
