5‐Methylcytosine Analysis of miRNAs in Minimal Change Disease

Minimal change disease (MCD) is a glomerular disorder, which is the most common cause of nephrotic syndrome in children. Additionally, the prevalence of MCD in adults has been increasing in recent years. During protein synthesis, noncoding RNAs can be regulated through a variety of modifications, which helps preserve biological diversity and complexity. This study aims to investigate the role of m5C-modified miRNAs in MCD, with the goal of identifying promising biomarkers and therapeutic targets for patients with this condition. Our findings revealed a substantial number of differentially modified m5C miRNAs in patients with MCD, predominantly exhibiting downregulation of modification. Notable miRNAs showing differential modification included miR-1282, miR-340-3p, miR-526b-3p, miR-3925-3p, and miR-511-5p. Further bioinformatics analysis demonstrated that the pathogenic mechanism of miR-511-5p in MCD may involve lipid metabolism by decreasing the expression of ectonucleotide pyrophosphatase/phosphodiesterase 4 (ENPP4) and ecto-nucleoside triphosphate diphosphohydrolase (ENTPD1). Both m5C writer and target genes had high-confidence interactions with miR-511-5p. This study confirmed the pathogenic role of m5C-modified miRNAs in MCD. The m5C modification of miRNAs in MCD is primarily downregulated, which is likely due to the downregulated of DNMT1. Finally, we focused on the downregulated m5C-modified miR-511-5p, which contributes to MCD by regulating metabolic pathways and decreasing the expression of ENPP4 and ENTPD1.