An integrated bioinformatics approach to identify key biomarkers in the tubulointerstitium of patients with focal segmental glomerulosclerosis and construction of mRNA–miRNA-lncRNA/circRNA networks

Objective The purpose of this study was to identify potential biomarkers in the tubulointerstitium of focal segmental glomerulosclerosis (FSGS) and comprehensively analyze its mRNA–miRNA-lncRNA/circRNA network.Methods The expression data (GSE108112 and GSE200818) were downloaded from the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/). Identification and enrichment analysis of differentially expressed genes (DEGs) were performed. the PPI networks of the DEGs were constructed and classified using the Cytoscape molecular complex detection (MCODE) plugin. Weighted gene coexpression network analysis (WGCNA) was used to identify critical gene modules. Least absolute shrinkage and selection operator regression analysis were used to screen for key biomarkers of the tubulointerstitium in FSGS, and the receiver operating characteristic curve was used to determine their diagnostic accuracy. The screening results were verified by quantitative real-time-PCR (qRT–PCR) and Western blot. The transcription factors (TFs) affecting the hub genes were identified by Cytoscape iRegulon. The mRNA–miRNA-lncRNA/circRNA network for identifying potential biomarkers was based on the starBase database.Results A total of 535 DEGs were identified. MCODE obtained eight modules. The green module of WGCNA had the greatest association with the tubulointerstitium in FSGS. PPARG coactivator 1 alpha (PPARGC1A) was screened as a potential tubulointerstitial biomarker for FSGS and verified by qRT–PCR and Western blot. The TFs FOXO4 and FOXO1 had a regulatory effect on PPARGC1A. The ceRNA network yielded 17 miRNAs, 32 lncRNAs, and 50 circRNAs.Conclusions PPARGC1A may be a potential biomarker in the tubulointerstitium of FSGS. The ceRNA network contributes to the comprehensive elucidation of the mechanisms of tubulointerstitial lesions in FSGS.