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

Abstract

BackgroundTo identify noninvasive diagnostic biomarkers for membranous nephropathy (MN).Material/MethodsThe mRNA microarray datasets GSE73953 using peripheral blood mononuclear cells (PBMCs) of 8 membranous nephropathy patients and 2 control patients; and microRNAs (miRNA) microarray dataset GSE64306 using urine sediments of 4 membranous nephropathy patients and 6 control patients were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were respectively identified from PBMCs and urine sediments of membranous nephropathy patients, followed with functional enrichment analysis, protein-protein interaction (PPI) analysis, and miRNA-target gene analysis. Finally, the DEGs and the target genes of DEMs were overlapped to obtain crucial miRNA-mRNA interaction pairs for membranous nephropathy.ResultsA total of 1246 DEGs were identified from PBMCs samples, among them upregulated CCL5 was found to be involved in the chemokine signaling pathway, and BAX was found to be apoptosis related; while downregulated PPM1A and CDK1 were associated with the MAPK signaling pathway and the p53 signaling pathway, respectively. The hub role of CDK1 (degree=18) and CCL5 (degree=12) were confirmed after protein-protein interaction network analysis in which CKD1 could interact with RAB1A. A total of 28 DEMs were identified in urine sediments. The 276 target genes of DEMs were involved in cell cycle arrest (PPM1A) and intracellular signal transduction (BRSK1). Thirteen genes were shared between the DEGs in PMBCs and the target genes of DEMs in urine sediments, but only hsa-miR-192-3p-RAB1A, hsa-miR-195-5p-PPM1A, and hsa-miR-328-5p-BRSK1 were negatively related in their expression level.ConclusionsBoth 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 by participating in inflammation and apoptosis.

MicroRNAs as Biomarkers for Nephrotic Syndrome

“…Zhang et al revealed the increased expression of urine miR-193a in MGN patients compared to healthy controls, and higher urine miR-193a levels were associated with poor renal survival [ 38 ]. Zhou et al conducted the microarray analysis and reported that serum and urine miR-195-5p, miR-192-3p, miR-328-5p levels and their target genes, PPM1A, RAB1A and BRSK1 may be the potential biomarkers for MGN [ 39 ]. Barbagallo et al analyzed miRNA profile and their target mRNAs from MGN kidney tissues and indicated that let-7a-5p, let-7b-5p, let-7c-5p, let-7d-5p, miR-107, miR-423-5p, miR-516-3p, miR-532-3p and miR-1275 levels were upregulated, and miR-129-3p levels were downregulated in MGN kidney samples compared to unaffected kidney tissues undergoing nephrectomy for renal cancer [ 40 ].…”

“…In spite of the accumulating evidence, most of these reports only analyzed specific miRNAs and there were only three reports in which comprehensive miRNA analysis by microarray was conducted [ 32 , 39 , 40 ]. In addition, most of these studies analyzing miRNAs have been compared MGN patients to healthy controls, not to other NS diseases, such as MCNS and FSGS, thus these miRNA profile changes might not be directly associated with MGN pathogenesis, but might be the common trend in NS patients.…”

Circ_0000524/miR‐500a‐5p/CXCL16 axis promotes podocyte apoptosis in membranous nephropathy

“…Many miRNAs play their function in MN by modulating gene expression 11,25,26 . Thus, we hypothesized that CXCL16 may be a potential target gene of miR‐500a‐5p and further participates in the circ_0000524‐mediated function in MN.…”

“…CircRNAs could act as microRNAs (miRNAs) sponges, thus leading to the inhibition of mRNAs in many diseases 7‐10 . Recently, miRNAs have been found to be biomarkers for the diagnosis and development of MN 2,11 . It has been revealed that miR‐500a‐5p inhibits cell growth in human colorectal cancer 12 .…”

Elevated miR‑195‑5p expression in deep vein thrombosis and mechanism of action in the regulation of vascular endothelial cell physiology

“…miR-195-5p has also been found to regulate hair follicle inductivity of dermal papilla cells by suppressing the activation of the Wnt/β-Catenin signaling pathway (32). Furthermore, it has been suggested that both peripheral blood and urinary miR-195-5p may be a potential biomarker for membranous nephropathy (33). All of these observations indicated that miR-195-5p is expressed differently under different pathophysiological conditions and that miR-195-5p plays a very important role in regulating cell growth.…”