M6A Modification and Transcription Analysis of LncRNA in Cerebral Ischemia/Reperfusion Injury

Jierong Mo, Zhiquan Li, Zhengfei Yang, Zuhua Huang, Pengpeng Guo, Jianfeng Gao, Haiqiong xiao, Ping Ye, Haini Qin, Tianen Zhou, Jun Jiang
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Abstract

LncRNA is a major factor in the occurrence and development of many diseases. However, its mechanism in cerebral ischemia/reperfusion injury (CIRI) is yet unknown. In this study, the transcriptional level and methylation modification level of LncRNAs before and after mechanical thrombectomy were compared by high-throughput sequencing. Venn diagram, Spearman correlation analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, TargetScan, and miRanda were used to analyze the experimental data. The results showed that four key LncRNAs changed at both transcription and methylation levels. Specifically, LncRNA FAR2, LINC02431, and AL357060.1 were downregulated and hypomethylated, while LncRNA FOXD2-AS1 was upregulated and hypomethylated. Moreover, positive regulation of angiogenesis, protein domain–specific binding, autophagy pathway, PPAR signaling pathway, and MAPK signaling pathway were co-enriched between LncRNAs with different expression levels and different methylation levels. Finally, a LncRNA-miRNA-mRNA network was constructed. Therefore, this study explored the potential key LncRNAs and regulatory mechanisms of CIRI.

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脑缺血再灌注损伤中 LncRNA 的 M6A 修饰和转录分析
LncRNA 是许多疾病发生和发展的主要因素。然而,其在脑缺血再灌注损伤(CIRI)中的作用机制尚不清楚。本研究通过高通量测序比较了机械性血栓切除术前后 LncRNA 的转录水平和甲基化修饰水平。实验数据采用维恩图、斯皮尔曼相关分析、基因本体(GO)、京都基因组百科全书(KEGG)富集分析、TargetScan和miRanda等方法进行分析。结果显示,四个关键的 LncRNA 在转录和甲基化水平上都发生了变化。具体来说,LncRNA FAR2、LINC02431和AL357060.1被下调和低甲基化,而LncRNA FOXD2-AS1被上调和低甲基化。此外,不同表达水平和不同甲基化水平的LncRNA之间还共同富集了对血管生成、蛋白结构域特异性结合、自噬通路、PPAR信号通路和MAPK信号通路的正向调控。最后,构建了一个 LncRNA-miRNA-mRNA 网络。因此,本研究探讨了 CIRI 潜在的关键 LncRNA 及其调控机制。
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Comparative and Functional Genomics
Comparative and Functional Genomics 生物-生化与分子生物学
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