Department of Minimally Invasive Hepatic Surgery, the First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang, China.
The First Department of General Surgery, the Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, China.
Epigenetics. 2023 Dec;18(1):2201716. doi: 10.1080/15592294.2023.2201716.
N6-Methyladenosine (mA) plays key roles in the regulation of biological functions and cellular mechanisms for ischaemia reperfusion (IR) injury in different organs. However, little is known about the underlying mechanisms of mA-modified mRNAs in hepatic IR injury. In mouse models, liver samples were subjected to methylated RNA immunoprecipitation with high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). In total, 16917 mA peaks associated with 4098 genes were detected in the sham group, whereas 21,557 mA peaks associated with 5322 genes were detected in the IR group. There were 909 differentially expressed mA peaks, 863 differentially methylated transcripts and 516 differentially mA modification genes determined in both groups. The distribution of mA peaks was especially enriched in the coding sequence and 3'UTR. Furthermore, we identified a relationship between differentially mA methylated genes (fold change≥1.5/≤ 0.667, value≤0.05) and differentially expressed genes (fold change≥1.5 and value≤0.05) to obtain three overlapping predicted target genes (Fnip2, Phldb2, and Pcf11). Our study revealed a transcriptome-wide map of mA mRNAs in hepatic IR injury and might provide a theoretical basis for future research in terms of molecular mechanisms.
N6-甲基腺苷（mA）在不同器官的缺血再灌注（IR）损伤中对调节生物功能和细胞机制起着关键作用。然而，关于 mA 修饰的 mRNA 在肝 IR 损伤中的潜在机制知之甚少。在小鼠模型中，对肝组织进行了甲基化 RNA 免疫沉淀与高通量测序（MeRIP-seq）和 RNA 测序（RNA-seq）。在假手术组中检测到 16917 个与 4098 个基因相关的 mA 峰，而在 IR 组中检测到 21557 个与 5322 个基因相关的 mA 峰。在两组中均有 909 个差异表达 mA 峰、863 个差异甲基化转录本和 516 个差异 mA 修饰基因。mA 峰的分布在编码序列和 3'UTR 中特别富集。此外，我们发现差异 mA 甲基化基因（fold change≥1.5/≤0.667， value≤0.05）和差异表达基因（fold change≥1.5 和 value≤0.05）之间存在关系，从而获得三个重叠的预测靶基因（Fnip2、Phldb2 和 Pcf11）。我们的研究揭示了肝 IR 损伤中 mA mRNAs 的全转录组图谱，可能为未来的分子机制研究提供理论基础。
