Epitranscriptomic profiling of m6A RNA methylation in renal epithelial tubular cells stimulated with calcium oxalate crystals through microarray analysis.

The aim of this study was to investigate the relationship of m6A RNA methylation to CaOX-induced renal tubular injury. Microarray analysis was performed to detect the difference in mRNA expression and m6A methylation between the injurious groups and controls. We established injurious renal tubular epithelial cell model induced by calcium oxalate crystals (CaOX), and we validated that CaOX could increase the overall m6A methylation levels. By microarray analysis, we identified 5967 differentially expressed mRNAs (2444 were up-regulated and 3523 were down-regulated in the injurious groups) and 6853 differentially methylated mRNAs (4055 were in hypermethylation and 3688 were in hypomethylation in the injurious groups). Four clusters (hyper-up, hyper-down, hypo-up and hypo-down) were further identified via conjoint analysis. Functional analysis revealed that m6A methylation played a crucial role in the development of CaOX through participating multiple processes covering inflammation, oxidative stress, apoptosis, crystal-cell adhesion. We delineated the first transcriptome-wide m6A landscape of injurious renal tubular cells in high-CaOX environment. We identified a series of mRNAs of renal tubular epithelial cells with differential expression and m6A methylation between the CaOX-treated groups and controls.