M6A-dependent regulation of microRNAs from CKD stage 5 patients: insights from epigenetic modification analysis

Chronic kidney disease (CKD) stage 5 is frequently accompanied by systemic inflammation, and peripheral blood mononuclear cells (PBMCs) play an important role. To define the epitranscriptomic features of PBMC small RNAs in CKD stage 5, we profiled N6-methyladenosine (m6A) using small RNA modification microarrays. A total of 158 miRNAs, 149 pre-miRNAs, and 197 tsRNAs showed differential m6A modification. Enrichment analysis implicated PI3K-Akt, p53 signalling, and leukocyte transendothelial migration. Integrating target prediction with GEO transcriptomic datasets identified IRF1 and RUNX2 as key targets. MeRIP confirmed reduced m6A in miR-205-3p and miR-93-5p, accompanied by upregulation of RUNX2 and downregulation of IRF1 by qPCR. These results define an altered m6A-modification profile of PBMC small RNAs in CKD stage 5 and highlight miRNA-target gene axes with potential biomarker utility.