Transcriptome -Wide m6A Methylome and Potential Drug Targets Prediction Analysis of Rheumatoid Arthritis

ABSTRACT: This research aims at assessing the m6A methylome in the RA peripheral blood mononuclear cells (PBMCs) and perform potential drug targets prediction analysis. Five RA samples and ten control samples were obtained from China-Japan Friendship Hospital. The various expression of m6A methylation and genes in RA and control group were compared with methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). Bioinformatics explorations were also made to explore the enriched biological roles and paths of the differentially expressed m6A methylation and genes. Potential drug targets prediction and validation were also constructed to provide potential therapeutic targets for RA. In total, 583 dysregulated m6A peaks, of which 295 were greatly upregulated and 288 were greatly downregulated, were identified. Similarly, 1570 differentially genes were acquired by RNA-seq, including 539 upregulated and 1031 downregulated. According to deeper joint exploration, the m6A methylation and mRNA expression degrees of 35 genes varied greatly, of which including 13 hyper-methylated as well as upregulated genes (hyper-up), 12 hyper-methylated and downregulated genes (hyper-down), 5 hypo-methylated as well as upregulated genes (hypo-up), and 5 hypo-methylated and downregulated genes (hypo-down) GO and KEGG explorations showed the enrichment of these distinct genes in “protein transport” “protein binding” and “lysosome”. In addition, the mRNA levels of TUBB2A, IGF2BP3, DYNC1I1 and FOSL1 were increased and consistent with the trend of our sequencing results. While after the treatment of TP and MTX, their mRNA levels were decreased. This research set up the transcriptional map of m6A in RA PBMCs and displayed the hidden association between RNA methylation alternation and associated genes in RA. The outcomes highlight the importance of m6A modification as a gene regulatory system in RA. Furthermore, TUBB2A, IGF2BP3, DYNC1I1 and FOSL1 might be potential therapeutic targets of TP and MTX during RA treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193193 | GEO | 2022/03/23

REPOSITORIES: GEO