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由m7G、m6A、m5C和m1A调控因子介导的RNA甲基化修饰模式在干燥综合征免疫微环境调节中的作用

Involvement of RNA methylation modification patterns mediated by m7G, m6A, m5C and m1A regulators in immune microenvironment regulation of Sjögren's syndrome.

作者信息

Liu Yuxiu, Zhu Jianing, Ding Lin

机构信息

People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, China.

Liaoning Aier Eye Hospital, Shenyang, Liaoning, China.

出版信息

Cell Signal. 2023 Jun;106:110650. doi: 10.1016/j.cellsig.2023.110650. Epub 2023 Mar 17.

DOI:10.1016/j.cellsig.2023.110650
PMID:36935085
Abstract

Keratoconjunctivitis is the most common complication of Sjögren's syndrome (SS). It has always been a hot research topic due to its complex pathogenesis. A further understanding of keratoconjunctiva xerosis can be obtained by studying the primary diseases. 7-Methylguanine (m7G), N6-methyladenosine (m6A), 5-methylcytosine (m5C), and N1-methyladenosine (m1A) are newly discovered epigenetic mechanisms involved in the development of SS. This study aimed to investigate the effects of m7G, m6A, m5C, and m1A modifications on the immune microenvironment of SS. Three microarray datasets were downloaded from the Gene Omnibus Expression (GEO) database, including 56 SS samples and 35 normal samples. Then, genes with m7G, m6A, m5C, and m1A methylation were explored, and the RNA modification patterns mediated by 59 m7G, m6A, m5C, and m1A regulators were summarized. The effects of m7G, m6A, m5C, and m1A modifications on immune infiltrating cells were discussed. Eukaryotic translation initiation factor 3 subunit D(EIF3D) was closely related to monocytes, and the expression of EIF3D was higher in SS with less monocytes. Two distinct patterns of RNA modification mediated by the 59 m7G, m6A, m5C, and m1A regulators were also identified, which infiltrated immune cells differently. Moreover, the two distinct RNA patterns were enriched in different signaling pathways, and their biological functions were explored. The findings revealed that m7G, m6A, m5C, and m1A modifications played vital roles in the diversity and complexity of the immune microenvironment in SS.

摘要

角结膜炎是干燥综合征(SS)最常见的并发症。由于其发病机制复杂,一直是研究的热点。通过研究原发性疾病可以进一步了解角结膜干燥症。7-甲基鸟嘌呤(m7G)、N6-甲基腺苷(m6A)、5-甲基胞嘧啶(m5C)和N1-甲基腺苷(m1A)是新发现的参与SS发病的表观遗传机制。本研究旨在探讨m7G、m6A、m5C和m1A修饰对SS免疫微环境的影响。从基因综合表达(GEO)数据库下载了三个微阵列数据集,包括56个SS样本和35个正常样本。然后,探索了具有m7G、m6A、m5C和m1A甲基化的基因,并总结了由59个m7G、m6A、m5C和m1A调节因子介导的RNA修饰模式。讨论了m7G、m6A、m5C和m1A修饰对免疫浸润细胞的影响。真核翻译起始因子3亚基D(EIF3D)与单核细胞密切相关,在单核细胞较少的SS中EIF3D表达较高。还确定了由59个m7G、m6A、m5C和m1A调节因子介导的两种不同的RNA修饰模式,它们对免疫细胞的浸润方式不同。此外,这两种不同的RNA模式在不同的信号通路中富集,并对其生物学功能进行了探索。研究结果表明,m7G、m6A、m5C和m1A修饰在SS免疫微环境的多样性和复杂性中起着至关重要的作用。

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