Changes of m6A methylation in renal tissue during cisplatin-induced acute injury.

Objective To investigate the role of N6-methyladenosine (m6A) methylation modification in the process of cisplatin-induced acute injury in mice. Methods·Four C57BL/6 mice were injected with cisplatin (20 mg/kg) through tail vein (the injury group); Another 4 C57BL/6 mice were injected with the same amount of saline (the control group). The changes of serum creatinine and urea nitrogen levels in the mice and the pathological injury in the renal tissue sections of the mice were evaluated to judge the success of the model. Methylated RNA immunoprecipitation (MeRIP) and RNA sequencing were used to detect the changes of m6A methylation and RNA expression in the kidney tissue of the two groups of mice. Gene ontology and Kyoto Encyclopedia of genes and genomes were used for visualization and comprehensive research. Transcriptome data and epigenetic data were combined to find candidate genes for pathological changes of cisplatin-induced acute injury. Results·Cisplatin could induce significant increase in the levels of serum creatinine and urea nitrogen compared with those in the baseline. Light microscope showed extensive tubular vacuolar degeneration, epithelial cell exfoliation and tubular necrosis, suggesting the success of modeling. MeRIP detection showed that a total of 2 277 genes contained 2 981 differentially expressed m6A methylation sites (expression multiple ≥2 and P<0.05) in the kidneys of mice in the injury group and the control group. These genes were mainly concentrated in the metabolic and cell death pathways. The joint analysis of genes expressing differential m6 A methylation sites and RNA differential expression genes found 1 002 genes with the same expression trend, such as fibrinogen α chain, solute carrier family 12 member 1 and hepatitis A virus cellular receptor 1. Conclusion Cisplatin can induce the change of methylation level of m6A methylation site on mRNA in renal tissue, and promote the process of acute renal injury. [ABSTRACT FROM AUTHOR]