Profiling analysis of circulating microRNA in peripheral blood of patients with class IV lupus nephritis

Abstract

Renal involvement in Systemic Lupus Erythematous (SLE) patients is one of the leading causes of morbidity and a significant contributor to mortality. It’s estimated that nearly 50% of SLE individuals develop kidney disease in the first year of the diagnosis. Class IV lupus nephritis (LN-IV) is the class of lupus nephritis most common in Colombian patients with SLE. Altered miRNAs expression levels have been reported in human autoimmune diseases including lupus. Variations in the expression pattern of peripheral blood circulating miRNAs specific for this class of lupus nephritis could be correlated with the pathophysiological status of this group of individuals. The aim of this study was to evaluate the relative abundance of circulating microRNAs in peripheral blood from Colombian patients with LN-IV. Circulating miRNAs in plasma of patients with diagnosis of LN-IV were compared with individuals without renal involvement (LNN group) and healthy individuals (CTL group). Total RNA was extracted from 10 ml of venous blood and subsequently sequenced using Illumina. The sequences were processed and these were analyzed using miRBase and Ensembl databases. Differential gene expression analysis was carried out with edgeR and functional analysis were done with DIANA-miRPath. Analysis was carried out using as variables of selection fold change (≥2 o ≤-2) and false discovery rate (0.05). We identified 24 circulating microRNAs with differential abundance between LN-IV and CTL groups, fourteen of these microRNAs are described for the first time to lupus nephritis (hsa-miR-589-3p, hsa-miR-1260b, hsa-miR-4511, hsa-miR-485-5p, hsa-miR-584-5p, hsa-miR-543, hsa-miR-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-4732-3p and hsa-miR-6741-3p). These changes in the abundance of miRNAs could be interpreted as alterations in the miRNAs-mRNA regulatory network in the pathogenesis of LN, preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards identifying disease biomarkers for early diagnosis of LN.

Circulating miRNA panels for specific and early detection in bladder cancer

“…Our miRNA microarray analysis clearly indicated that miR‐6087 expression was statistically significantly decreased in patients with bladder cancer, although the molecular mechanism of the downregulation of miR‐6087 remains unclear. One report showed miR‐6087 detection in patients with class IV lupus nephritis, which is commonly developed in patients with systemic lupus erythematous in the Colombian population . In the paper, Navarro‐Quiroz et al show the upregulation of miR‐6087 in serum samples of patients with lupus nephritis.…”

Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy

“…In addition, we described for the first time that miR-760, miR-3677-3p, miR-548ah-3p, miR-548p, miR-320e, and miR-23c were up-regulated in the DN patients. Although miR-133a-3p and miR-153-3p have been reported to have implications in pig kidneys [24] and lupus nephritis [25], this is the first time they were reported in the nephrotic DN patients.…”

Altered expression of exosomal miRNAs from primary human trabecular meshwork cells induced by transforming growth factor-β2

“…were the top three up-regulated exosomal miRNAs, whereas hsa-miR-6800-3p, hsa-miR-6716-3p, and hsa-let-7i-5p were revealed to be markedly down-regulated. Hsa-miR-6087 has been previously reported to act as an important mediators of cancer [44,45],intermediate monocytes [46]and regulation of cell differentiation [47]. Has-miR-663a is located in the chromosome 20q11.1 and has been reported to be closely related with the biological behavior of cell differentiation, inflammation, autoimmune diseases, and cancer [48][49][50].…”