Potential Target Analysis of Triptolide Based on Transcriptome-Wide m6A Methylome in Rheumatoid Arthritis

作者：Danping Fan, Bin Liu, Xiaofeng Gu, Qian Zhang, Qinbin Ye, Xiaoyu Xi, Ya Xia, Qiong Wang, Zheng Wang, Bailiang Wang, Yuan Xu, Cheng Xiao · 发表于：Frontiers in Pharmacology · 年份：2022 · DOI：10.3389/fphar.2022.843358 · 被引用次数：27 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Cancer-related gene regulation

Triptolide (TP), a major active component of the herb Tripterygium wilfordii Hook F (TwHF), has been shown to exert therapeutic potential against rheumatoid arthritis (RA). However, its molecular mechanism of action has not been fully elucidated. This study aimed to analyze the potential target of TP based on the discovery of differentially methylated and expressed genes (DMEGs) in RA using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). Five RA samples and ten control samples were obtained from China-Japan Friendship Hospital. The various levels of m 6 A methylation and genes expressed in the RA and control groups were compared by MeRIP-seq and RNA-seq. Bioinformatics explorations were also performed to explore the enriched biological roles and paths of the differentially expressed m 6 A methylation and genes. Molecular networks between TP target proteins and DMEGs were performed using Ingenuity Pathway Analysis (IPA) software. Potential target of TP was determined with Gene Expression Omnibus (GEO) database mining, molecular docking, and in vitro experiment validation. In total, 583 dysregulated m 6 A peaks, of which 295 were greatly upregulated and 288 were greatly downregulated, were identified. Similarly, 1,570 differentially expressed genes were identified by RNA-seq, including 539 upregulated and 1,031 downregulated genes. According to the deeper joint exploration, the m 6 A methylation and mRNA expression degrees of 35 genes var...