Bioinformatic investigation for candidate genes and molecular mechanism in the pathogenesis of membranous nephropathy.

We aimed to explore the detailed molecular mechanism of immune-associated genes in membranous nephropathy (MN). A microarray data set (GSE133288) was retrieved from the Gene Expression Omnibus database. Differentially expressed mRNAs (DEMs) in MN vs control groups were identified, and MN-related DEMs (MN-DEMs) were further verified and screened using the comparative toxicogenomics database (CTD) database. The publicly available database, InnateDB was used to investigate immune genes, and the overlapped genes between MN-DEMs and the immune genes were considered as MN-related immune genes (iDEMs). A protein-protein interaction network (PPI) was constructed based on these iDEMs, followed by function and pathway enrichment analysis. Finally, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) associated with iDEMs were predicted, followed by a lncRNA-miRNA-mRNA (competing endogenous RNAs, ceRNA) network construction. A total of 327 DEMs and 48 iDEMs were revealed; a PPI network was constructed with 100 PPI pairs and 37 iDEMs. iDEMs including JUN and FOS were mainly enriched in pathways such as osteoclast differentiation and function including response to immobilization stress, respectively. Based on mRNA-associated miRNA and lncRNA prediction, 30 ceRNA interactions including KCNQ1OT1-miR-204-5p-SRY-Box Transcription Factor 4 (SOX4) were explored. mRNAs including FOS and JUN might participate in MN development via response to immobilization stress function and the osteoclast differentiation pathway. The mRNA SOX4 might contribute to MN progression via sponging KCNQ1OT1-miR-204-5p interaction.

Li P ，Zhong X ，Zhang L ，Yu Y ，Niu J ... -  《-》

Both Peripheral Blood and Urinary miR-195-5p, miR-192-3p, miR-328-5p and Their Target Genes PPM1A, RAB1A and BRSK1 May Be Potential Biomarkers for Membranous Nephropathy.

Zhou G ，Zhang X ，Wang W ，Zhang W ，Wang H ，Xin G ... -  《MEDICAL SCIENCE MONITOR》

Biomarker Identification in Membranous Nephropathy Using a Long Non-coding RNA-Mediated Competitive Endogenous RNA Network.

This study was aimed to identify biomarker associated with membranous nephropathy (MN) progression by integration of expression profiles and competitive endogenous RNA (ceRNA) network analysis. The gene (GSE108113) and microRNAs (miRNAs) expression profiles (GSE64306) were downloaded to identify the differentially expressed mRNAs, miRNAs and long non-coding RNAs (lncRNAs) between MN and control groups. The functions and pathways enriched by the differentially expressed mRNAs were analyzed. The mRNA-lncRNA co-expression network was constructed followed by and the ceRNA network construction. Total 264 upregulated and 196 downregulated differentially expressed mRNAs, 79 upregulated and 4 downregulated lncRNAs, as well as 115 upregulated and 93 downregulated miRNAs were obtained between MN and control groups. After analysis, the differential mRNAs were significantly involved in multiple immune-related processes, and cell proliferation, apoptosis and differentiation processes, as well as pathways of taste transduction and lysosome. Finally, a ceRNA network consisting of 4 mRNAs (EPB41L5, FAM43A, PRKG1 and TTC14), 3 lncRNAs (LINC00052, LINC00641 and N4BP2L2-IT2) and 5 miRNAs (hsa-miR-145-5p, hsa-miR-3605-5p, hsa-miR-148a-3p, hsa-miR-497-5p and hsa-miR-148b-3p) was constructed. Our study indicated dysregulation of immune- and apoptosis-associated functions and taste transduction and lysosome pathways may play important roles in MN progression. Deregulated ceRNAs, such as LINC00052-hsa-miR-145-5p-EPB41L5, LINC00052-hsa-miR-148a-3p-FAM43A and LINC00641-hsa-497-5p-PRKG1, may be associated with MN development.

Zhou G ，Jiang N ，Zhang W ，Guo S ，Xin G ... -  《-》

Biomarker prediction for membranous nephropathy prognosis by microarray analysis.

This study aimed to explore biomarkers for membranous nephropathy (MN) diagnosis and to provide novel insights into the pathogenesis of this disease. A microarray data set, GSE73953, was used, which contained 15 immunoglobulin A nephropathy (IgAN) samples, 8 MN samples and 2 healthy controls. Pretreatments were performed for the raw data, and then, the differentially expressed genes (DEG) were screened out using the limma package. The function and pathways of these genes were demonstrated through enrichment analysis. Protein-protein interaction (PPI) network analysis was performed to uncover interactions of DEG from the protein level. MN-related genes were further selected, integrating the Comparative Toxicogenomics Database (CTD). In total, 446 and 231 DEG were identified in the comparisons of MN versus control and MN versus IgAN, respectively. JUN, NFKB1, TGFB1 and PPBP were the predominant DEG, and the latter two were especially differentially expressed between the MN and IgAN groups. UBL4A and EIF4G1 were the two most important DEG for MN because they were downregulated compared with both control and IgAN groups. The above-mentioned genes were highlighted in the PPI networks and mainly enriched the ribosome- and platelet-related function/pathways. Several potential biomarkers were identified in MN, and some of them could well distinguish the MN from IgAN. Disruption of ribosome- and platelet-related function or pathways might contribute to MN progression. EIF4F and UBL4A might be two novel biomarkers for MN prognosis. Nevertheless, more experimental validations are needed.

Zhou G ，Xin G ，Zhang W ，Zhang X ... -  《-》

Bioinformatic Analysis Reveals Novel Immune-Associated Hub Genes in Human Membranous Nephropathy.

Tang W ，Wang Z ，Cao Y ，Zhang D ，Mi X ... -  《-》