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

Overview

Journal Med Sci Monit

Specialties General Medicine
Pathology

Date 2019 Mar 14

PMID 30865617

Citations 12

Authors

Guangyu Zhou

Xiaofei Zhang

Wanning Wang

Wenlong Zhang

Huaying Wang

Guangda Xin

Affiliations

Soon will be listed here.

Abstract

BACKGROUND To identify noninvasive diagnostic biomarkers for membranous nephropathy (MN). MATERIAL AND METHODS The 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. RESULTS A 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. CONCLUSIONS 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 by participating in inflammation and apoptosis.

Citing Articles

Bibliometric and visual analysis of membranous nephropathy literature from 2010 to 2023.

Chen Y, Liu C, Shen H, Su P, Pang L, Zeng C Front Pharmacol. 2024; 15:1426897.

PMID: 39329128 PMC: 11424533. DOI: 10.3389/fphar.2024.1426897.

Roles of microRNA-192 in diabetic nephropathy: the clinical applications and mechanisms of action.

Wan X, Liao J, Lai H, Zhang S, Cui J, Chen C Front Endocrinol (Lausanne). 2023; 14:1179161.

PMID: 37396169 PMC: 10309560. DOI: 10.3389/fendo.2023.1179161.

Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway.

Wang J, Shang B, Tang L, Tian M, Liu J Open Med (Wars). 2023; 18(1):20220615.

PMID: 36969728 PMC: 10037167. DOI: 10.1515/med-2022-0615.

An integrated co-expression network analysis reveals novel genetic biomarkers for immune cell infiltration in chronic kidney disease.

Xia J, Hou Y, Cai A, Xu Y, Yang W, Huang M Front Immunol. 2023; 14:1129524.

PMID: 36875100 PMC: 9981626. DOI: 10.3389/fimmu.2023.1129524.

MicroRNAs: Potential mediators between particulate matter 2.5 and Th17/Treg immune disorder in primary membranous nephropathy.

Zhou X, Dai H, Jiang H, Rui H, Liu W, Dong Z Front Pharmacol. 2022; 13:968256.

PMID: 36210816 PMC: 9532747. DOI: 10.3389/fphar.2022.968256.

References

Kanehisa M, Goto S . KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999; 28(1):27-30. PMC: 102409. DOI: 10.1093/nar/28.1.27. View

Ashburner M, Ball C, Blake J, Botstein D, Butler H, Cherry J . Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000; 25(1):25-9. PMC: 3037419. DOI: 10.1038/75556. View

Takaya K, Koya D, Isono M, Sugimoto T, Sugaya T, Kashiwagi A . Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells. Am J Physiol Renal Physiol. 2003; 284(5):F1037-45. DOI: 10.1152/ajprenal.00230.2002. View

Bader G, Hogue C . An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics. 2003; 4:2. PMC: 149346. DOI: 10.1186/1471-2105-4-2. View

Irizarry R, Hobbs B, Collin F, Beazer-Barclay Y, Antonellis K, Scherf U . Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003; 4(2):249-64. DOI: 10.1093/biostatistics/4.2.249. View

Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View

Eiro M, Katoh T, Watanabe T . Risk factors for bleeding complications in percutaneous renal biopsy. Clin Exp Nephrol. 2005; 9(1):40-5. DOI: 10.1007/s10157-004-0326-7. View

de Haij S, Bakker A, van der Geest R, Haegeman G, Vanden Berghe W, Aarbiou J . NF-kappaB mediated IL-6 production by renal epithelial cells is regulated by c-jun NH2-terminal kinase. J Am Soc Nephrol. 2005; 16(6):1603-11. DOI: 10.1681/ASN.2004090781. View

Santamaria D, Barriere C, Cerqueira A, Hunt S, Tardy C, Newton K . Cdk1 is sufficient to drive the mammalian cell cycle. Nature. 2007; 448(7155):811-5. DOI: 10.1038/nature06046. View

10.

Sun W, Yu Y, Dotti G, Shen T, Tan X, Savoldo B . PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation. Cell Signal. 2008; 21(1):95-102. PMC: 2658596. DOI: 10.1016/j.cellsig.2008.09.012. View

11.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

12.

Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P . The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 2010; 39(Database issue):D561-8. PMC: 3013807. DOI: 10.1093/nar/gkq973. View

13.

Chen Y, Wang X, Yao X, Zhang D, Yang X, Tian S . Abated microRNA-195 expression protected mesangial cells from apoptosis in early diabetic renal injury in mice. J Nephrol. 2011; 25(4):566-76. DOI: 10.5301/jn.5000034. View

14.

Zheng R, Deng Y, Chen Y, Fan J, Zhang M, Zhong Y . Astragaloside IV attenuates complement membranous attack complex induced podocyte injury through the MAPK pathway. Phytother Res. 2011; 26(6):892-8. DOI: 10.1002/ptr.3656. View

15.

Chen Y, Wang X, Yao X, Zhang D, Yang X, Tian S . MicroRNA-195 promotes apoptosis in mouse podocytes via enhanced caspase activity driven by BCL2 insufficiency. Am J Nephrol. 2011; 34(6):549-59. DOI: 10.1159/000333809. View

16.

Li R, Gong Z, Pan C, Xie D, Tang J, Cui M . Metal-dependent protein phosphatase 1A functions as an extracellular signal-regulated kinase phosphatase. FEBS J. 2013; 280(11):2700-11. DOI: 10.1111/febs.12275. View

17.

Nawaz F, Larsen C, Troxell M . Membranous nephropathy and nonsteroidal anti-inflammatory agents. Am J Kidney Dis. 2013; 62(5):1012-7. DOI: 10.1053/j.ajkd.2013.03.045. View

18.

Chen W, Lin X, Huang J, Tan K, Chen Y, Peng W . Integrated profiling of microRNA expression in membranous nephropathy using high-throughput sequencing technology. Int J Mol Med. 2013; 33(1):25-34. PMC: 3868500. DOI: 10.3892/ijmm.2013.1554. View

19.

Jenkins R, Davies L, Taylor P, Akiyama H, Cumbes B, Beltrami C . miR-192 induces G2/M growth arrest in aristolochic acid nephropathy. Am J Pathol. 2014; 184(4):996-1009. DOI: 10.1016/j.ajpath.2013.12.028. View

20.

Simard-Meilleur M, Troyanov S, Roy L, Dalaire E, Brachemi S . Risk factors and timing of native kidney biopsy complications. Nephron Extra. 2014; 4(1):42-9. PMC: 4000304. DOI: 10.1159/000360087. View