Xu Rui, Yan Changshun, Cao GuiQiu
Department of Cardiology, Fifth Affiliated Hospital of Xinjiang Medical University, China.
Department of Cardiology, Fifth Affiliated Hospital of Xinjiang Medical University, China.
Clinics (Sao Paulo). 2025 May 22;80:100677. doi: 10.1016/j.clinsp.2025.100677. eCollection 2025.
The circadian system plays a crucial role in managing cardiovascular functions, with disturbances in this system associated with Myocardial Infarction (MI). Despite this connection, the exact mechanisms by which clock genes influence MI occurrence are not well-defined. This research focused on investigating the link between clock genes and MI.
The authors examined MI microarray datasets (GSE151412 and GSE60993) from the GEO database, concentrating on Differentially Expressed Genes (DEGs) associated with the circadian system. To clarify critical biological functions and pathways, the authors performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Through Lasso regression, the authors pinpointed hub genes and confirmed their relevance using both the GSE66360 dataset and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Furthermore, the authors conducted single-Gene Set Enrichment Analysis (GSEA) to reveal pathways linked to the hub gene. The analysis extended to exploring drug interactions and networks involving competing endogenous RNA (ceRNA).
The present analysis identified ten clock genes associated with circadian rhythms that showed differential expression between MI patients and healthy controls. Enrichment analysis suggested these genes' roles in pathways like the Gap junction and circadian rhythm pathways. Following Lasso regression and validation, RPS27A was identified as the main hub gene. GSEA further highlighted enriched pathways, such as mismatch repair. Additionally, immune infiltration analysis revealed notable differences in B-cell and CD4+ T-cell populations between the MI group and the control group.
The present findings suggest that the clock-related gene RPS27A is associated with MI, potentially influencing its development through circadian rhythm regulation. These results enhance the understanding of MI pathogenesis and may offer new avenues for therapeutic intervention.
昼夜节律系统在心血管功能管理中起着至关重要的作用，该系统的紊乱与心肌梗死（MI）相关。尽管存在这种联系，但时钟基因影响MI发生的确切机制尚不清楚。本研究聚焦于调查时钟基因与MI之间的联系。
作者检查了来自基因表达综合数据库（GEO）的MI微阵列数据集（GSE151412和GSE60993），重点关注与昼夜节律系统相关的差异表达基因（DEG）。为了阐明关键的生物学功能和途径，作者使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）进行了富集分析。通过套索回归，作者确定了枢纽基因，并使用GSE66360数据集和定量逆转录聚合酶链反应（qRT-PCR）证实了它们的相关性。此外，作者进行了单基因集富集分析（GSEA）以揭示与枢纽基因相关的途径。该分析还扩展到探索涉及竞争性内源性RNA（ceRNA）的药物相互作用和网络。
本分析确定了十个与昼夜节律相关的时钟基因，这些基因在MI患者和健康对照之间表现出差异表达。富集分析表明这些基因在间隙连接和昼夜节律途径等途径中的作用。经过套索回归和验证，RPS27A被确定为主要枢纽基因。GSEA进一步突出了富集的途径，如错配修复。此外，免疫浸润分析显示MI组和对照组之间B细胞和CD4 + T细胞群体存在显著差异。
本研究结果表明，与时钟相关的基因RPS27A与MI相关，可能通过昼夜节律调节影响其发展。这些结果加深了对MI发病机制的理解，并可能为治疗干预提供新途径。
