Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.
Department of Scientific Research, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Medicine (Baltimore). 2023 Mar 10;102(10):e33133. doi: 10.1097/MD.0000000000033133.
N6-methyladenosine (m6A) RNA methylation, as a reversible epigenetic modification of mammalian mRNA, holds a critical role in multiple biological processes. m6A modification in Long non-coding RNAs (lncRNAs) has increasingly attracted more attention in recent years, especially in diabetics, with or without metabolic syndrome. We investigated via m6A-sequencing and RNA-sequencing the differentially expressed m6A modification lncRNAs by high glucose and TNF-α induced endothelial cell dysfunction in human umbilical vein endothelial cells. Additionally, gene ontology and kyoto encyclopedia of genes and genomes analyses were performed to analyze the biological functions and pathways for the target of mRNAs. Lastly, a competing endogenous RNA network was established to further reveal a regulatory relationship between lncRNAs, miRNAs and mRNAs. A total of 754 differentially m6A-methylated lncRNAs were identified, including 168 up-regulated lncRNAs and 266 down-regulated lncRNAs. Then, 119 significantly different lncRNAs were screened out, of which 60 hypermethylated lncRNAs and 59 hypomethylated lncRNAs. Moreover, 122 differentially expressed lncRNAs were filtered, containing 14 up-regulated mRNAs and 18 down-regulated lncRNAs. Gene ontology and kyoto encyclopedia of genes and genomes analyses analyses revealed these targets were mainly associated with metabolic process, HIF-1 signaling pathway, and other biological processes. The competing endogenous RNA network revealed the regulatory relationship between lncRNAs, miRNAs and mRNAs, providing potential targets for the treatment and prevention of diabetic endothelial cell dysfunction. This comprehensive analysis for lncRNAs m6A modification in high glucose and TNF-α-induced human umbilical vein endothelial cells not only demonstrated the understanding of characteristics of endothelial cell dysfunction, but also provided the new targets for the clinical treatment of diabetes. Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.
N6-甲基腺苷（m6A）RNA 甲基化作为哺乳动物 mRNA 的一种可逆的表观遗传修饰，在多种生物学过程中起着关键作用。近年来，长非编码 RNA（lncRNA）中的 m6A 修饰越来越受到关注，尤其是在糖尿病患者中，无论是否合并代谢综合征。我们通过 m6A 测序和 RNA 测序，研究了高糖和 TNF-α诱导人脐静脉内皮细胞功能障碍时，lncRNA 中差异表达的 m6A 修饰。此外，还进行了基因本体论和京都基因与基因组百科全书分析，以分析 mRNAs 靶标的生物学功能和途径。最后，建立了竞争性内源性 RNA 网络，以进一步揭示 lncRNA、miRNA 和 mRNAs 之间的调控关系。共鉴定出 754 个差异 m6A 甲基化的 lncRNA，包括 168 个上调的 lncRNA 和 266 个下调的 lncRNA。然后，筛选出 119 个差异显著的 lncRNA，其中 60 个高甲基化的 lncRNA 和 59 个低甲基化的 lncRNA。此外，筛选出 122 个差异表达的 lncRNA，其中包括 14 个上调的 mRNAs 和 18 个下调的 lncRNA。基因本体论和京都基因与基因组百科全书分析表明，这些靶标主要与代谢过程、HIF-1 信号通路和其他生物学过程有关。竞争性内源性 RNA 网络揭示了 lncRNA、miRNA 和 mRNAs 之间的调控关系，为糖尿病内皮细胞功能障碍的治疗和预防提供了潜在的靶点。本研究对高糖和 TNF-α诱导的人脐静脉内皮细胞中 lncRNA 的 m6A 修饰进行了全面分析，不仅加深了对内皮细胞功能障碍特征的认识，还为糖尿病的临床治疗提供了新的靶点。个人的隐私信息不会被公布。本系统综述也不会危及参与者的权利。不需要伦理批准。研究结果可能会发表在同行评议的期刊上，或在相关会议上传播。
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