Small RNA deep sequencing reveals novel miRNAs in peripheral blood mononuclear cells from patients with IgA nephropathy

Mol Med Rep. 2020 Oct;22(4):3378-3386. doi: 10.3892/mmr.2020.11405. Epub 2020 Aug 3.

Abstract

Peripheral blood mononuclear cells (PBMCs) contribute to the deposition of immunoglobulin A (IgA) and progression of IgA nephropathy (IgAN). This study was performed to identify novel microRNAs (miRNAs/miRs) associated with IgAN. Small RNAs were isolated from PBMCs collected from 10 healthy participants and 10 patients with IgAN; the RNAs were then subjected to high‑throughput small RNA sequencing. The results showed that miRNAs constituted 70.33 and 69.83% of small RNAs in PBMCs from healthy participants and patients with IgAN, respectively. In total, 44 differentially expressed miRNAs were identified, of which 34 were upregulated and 10 were downregulated. Among these differentially expressed miRNAs, most showed novel associations with IgAN, except miR‑148a‑3p, miR‑184 and miR‑200a. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes of the differentially expressed miRNAs were primarily enriched in cancer pathways, the PI3K‑Akt signaling pathway and MAPK pathways, all of which control cell proliferation and gene expression. Moreover, miR‑3121‑3p, miR‑203a‑3p and miR‑200a‑3p may regulate core 1 synthase, glycoprotein‑N‑acetylgalactosamine 3‑β‑galactosyltransferase 1 (C1GALT1) expression by binding to its 3' untranslated region. In conclusion, 44 differentially expressed miRNAs were discovered, 41 of which were newly found to be associated with IgAN. The differentially expressed miRNAs may regulate the progression of IgAN by controlling the behavior of PBMCs or deposition of IgA via targeting of signaling pathways or expression of C1GALT1. These findings may provide a basis for further research regarding IgAN diagnosis and therapy.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Cell Proliferation
  • Female
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Glomerulonephritis, IGA / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Leukocytes, Mononuclear / chemistry*
  • Male
  • MicroRNAs / genetics*
  • Sequence Analysis, RNA / methods*
  • Young Adult

Substances

  • MicroRNAs