Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, China.
Fourth Clinical Medical College, Xinjiang Medical University, Ürümqi, China.
Front Immunol. 2023 Mar 28;14:1137195. doi: 10.3389/fimmu.2023.1137195. eCollection 2023.
Chronic obstructive pulmonary disease (COPD), a common respiratory disease, can be divided into stable phase and acute exacerbation phase (AECOPD) and is characterized by inflammation and hyper-immunity. Methylation of N6-methyladenosine (m6A) is an epigenetic modification that regulates the expression and functions of genes by influencing post-transcriptional RNA modifications. Its influence on the immune regulation mechanism has attracted great attention. Herein, we present the m6Amethylomic landscape and observe how the methylation of m6A participates in the pathological process of COPD. The m6A modification of 430 genes increased and that of 3995 genes decreased in the lung tissues of mice with stable COPD. The lung tissues of mice with AECOPD exhibited 740 genes with hypermethylated m6A peak and 1373 genes with low m6A peak. These differentially methylated genes participated in signaling pathways related to immune functions. To further clarify the expression levels of differentially methylated genes, RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequencing data were jointly analyzed. In the stable COPD group, 119 hypermethylated mRNAs (82 upregulated and 37 downregulated mRNAs) and 867 hypomethylated mRNAs (419 upregulated and 448 downregulated mRNAs) were differentially expressed. In the AECOPD group, 87 hypermethylated mRNAs (71 upregulated and 16 downregulated mRNAs) and 358 hypomethylated mRNAs (115 upregulated and 243 downregulated mRNAs) showed differential expression. Many mRNAs were related to immune function and inflammation. Together, this study provides important evidence on the role of RNA methylation of m6A in COPD.
慢性阻塞性肺疾病（COPD）是一种常见的呼吸系统疾病，可分为稳定期和急性加重期（AECOPD），其特征为炎症和超免疫。N6-甲基腺苷（m6A）的甲基化是一种表观遗传修饰，通过影响转录后 RNA 修饰来调节基因的表达和功能。其对免疫调节机制的影响引起了广泛关注。在此，我们展示了 m6A 甲基组学图谱，并观察了 m6A 甲基化如何参与 COPD 的病理过程。在稳定期 COPD 小鼠的肺组织中，430 个基因的 m6A 修饰增加，3995 个基因的 m6A 修饰减少。AECOPD 小鼠的肺组织中，有 740 个基因的 m6A 峰出现超甲基化，1373 个基因的 m6A 峰出现低甲基化。这些差异甲基化基因参与了与免疫功能相关的信号通路。为了进一步阐明差异甲基化基因的表达水平，联合分析了 RNA 免疫沉淀测序（MeRIP-seq）和 RNA-seq 数据。在稳定期 COPD 组中，有 119 个高甲基化 mRNAs（82 个上调和 37 个下调 mRNAs）和 867 个低甲基化 mRNAs（419 个上调和 448 个下调 mRNAs）表现出差异表达。在 AECOPD 组中，有 87 个高甲基化 mRNAs（71 个上调和 16 个下调 mRNAs）和 358 个低甲基化 mRNAs（115 个上调和 243 个下调 mRNAs）表现出差异表达。许多 mRNAs 与免疫功能和炎症有关。总之，本研究为 m6A RNA 甲基化在 COPD 中的作用提供了重要证据。
