文献类型：期刊文献

英文题名：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

作者：Zhang, Yun Xia[1,2];Bai, Jun Yuan[1,3];Pu, Xiaowei[1];Lv, Juan[1,2];Dai, En Lai[1]

第一作者：Zhang, Yun Xia;张芸霞

通信作者：Dai, EL[1]

机构：[1]Gansu Univ Tradit Chinese Med, Coll Integrated Tradit & Western Med, Lanzhou 730000, Peoples R China;[2]Gansu Prov Hosp Tradit Chinese Med, Lanzhou, Peoples R China;[3]Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Tradit Chinese Med, Coll Integrated Tradit & Western Med, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2023

卷号：45

期号：2

外文期刊名：RENAL FAILURE

收录：;Scopus(收录号：2-s2.0-85178044139);WOS:【SCI-EXPANDED(收录号:WOS:001118071400001)】；

基金：This work was supported by the National Science Foundation of China (82160852).

语种：英文

外文关键词：Focal segmental glomerulosclerosis; tubulointerstitium; weighted gene coexpression network analysis; least absolute shrinkage and selection operator; PPARGC1A; mRNA-miRNA-lncRNA/circRNA network

摘要：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.