Identification of candidate microRNA biomarkers in renal fibrosis: a meta-analysis of profiling studies

Abstract

The prognostic, diagnostic and therapeutic value of microRNA (miRNA) expression aberrations in renal fibrosis has been studied in recent years. However, the miRNA expression profiling efforts have led to inconsistent results between the studies. The aim of this study was to perform a meta-analysis on the renal fibrosis miRNA expression profiling studies to identify candidate diagnostic biomarkers. We performed comprehensive literature searches in several databases to identify miRNA expression studies of renal fibrosis in animal models and humans. The miRNAs expression data were extracted from 20 included studies, and both miRNA vote-counting strategy and Robust Rank Aggregation method were utilized to identify significant miRNA meta-signatures. The predicted and validated targets of miRNA meta-signature were obtained by using MultiMiR package in 11 databases. Then a gene set enrichment analysis (KEGG, PANTHER pathways and GO processes) were carried out with GeneCodis web tool to recognize pathways that are most strongly influenced by modified expressions of these miRNAs. We recognized in both meta-analysis approaches a significant miRNA meta-signature of five up-regulated (miR-142-3p, miR-223-3p, miR-21-5p, miR-142-5p and miR-214-3p) and two down-regulated (miR-29c-3p and miR-200a-3p) miRNAs. Enrichment analysis confirmed that miRNA meta-signature cooperatively target functionally related genes in signalling and developmental pathways in renal fibrosis. This meta-analysis identified seven highly significant and consistently dysregulated miRNAs from 20 datasets, as the focus of future investigations to discover their potential influence to renal fibrosis and their clinical utility as biomarkers and/or as therapeutic mediators against chronic kidney disease..

Bioinformatic Analyses of Renal Ischaemia-Reperfusion Injury Models: Identification of Key Genes Involved in the Development of Kidney Disease

“…In the downregulated network, miR-181a, miR-181b, miR-181c and miR-181d were predicted to regulate Mat2a, Timp3 and Igsf11. Among these miRNAs, miR-142-5p was identified as a candidate biomarker of renal fibrosis [38]. miR-181a was documented to mediate cell apoptosis in cisplatin-treated HK-2 cells [39].…”

Potential role of ACE2-related microRNAs in COVID-19-associated nephropathy

“…Exosomes in urine are reliable tool for the analysis of miRNAs in kidney diseases, since many miRNAs originated from the kidney cells [ 87 ]. The expression of various miRNAs are dysregulated in different kidney conditions, for instance, the aberrations of miRNA expression in kidney fibrosis was described in a recent meta-analysis, identifying five upregulated (miR-142–3p, miR-223–3p, miR-21–5p, miR-142–5p, miR-214–3p) and two downregulated (miR-29c-3p, miR-200a-3p) miRNAs [ 120 ].…”

“…Gu et al conducted a miRNAs study using hypertensive rats, and found that chronic aerobic exercise training improved RAAS balance, decreased blood pressure by down-regulation of the expression of miR-143. The result was accompanied by significantly elevated circulating ACE2 and angiotensin (1–7) levels [ 120 , 121 ]. Another study conducted by Lambert et al showed that miR-421 (located on chromosome X q13.2) could decrease the ACE2 protein expression by translational repression [ 128 , 137 , 21 ].…”

“…While mir-19b, −29, −132, −181, and −212 have relative evidence as gene silencer. The mir-29 has a strong evidence as fibrotic-protecting miRNA [ 108 , 120 , 126 , 33 , [141] , [142] , [143] , [144] , [145] , [146] , [147] ]. The upregulation of miR-130 is reported in relapsing INS, however, its target is on GAX, a growth arrest-specific homeobox, which inhibits proliferation, differentiation, and migration of VSMCs ( Table 1 ).…”

Epigenetic Modification Mechanisms Involved in Inflammation and Fibrosis in Renal Pathology

“…In any case, a recent review about miRNA in patients with diabetic kidney disease identified miR-21-5p, miR-29a-3p, miR-126-3p, miR-192-5p, miR-214-3p, and miR-342-3p that are consistently dysregulated among different studies, and bioinformatics analysis revealed that all of them play essential roles in diabetic kidney disease. Finally, a recent meta-analysis from 20 datasets from human and animal studies is aimed at recognizing consistently dysregulated miRNAs in renal fibrosis and identifying 5 upregulated and 2 downregulated miRNA [166]. Thus, miR-1423p, miR-2233p, miR-215p, miR-1425p, and miR-2143p were shown to be consistently upregulated in several reports, whereas miR-29c-3p and miR-200a-3p were downregulated.…”