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Data from the three murine lupus-like models analyzed | Data from SLE and other autoimmune diseases |
Deregulated miRNAs | Fold change | Targeted gene | Gene function | Possible effects |
mArray | RTPCR |
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▼ miR-155-5p | 0.51 | 0.43 | SFPI1 (SPI1) | Impairs class-switch DNA recombination and plasma cell differentiation. | Reduction of B cell activation [28]. |
SHIP-1 | Negative regulator of B cell activation. | Reduction of high-affinity IgG 1 antibodies [33]. |
AICDA | Higher mutation frequency involved in somatic hypermutation. | B cell activation and production of high-affinity IgG 1 antibodies [34, 48]. |
SMAD2/EP300c | Transcription factor complex (TFC) triggered by TGF-β signaling. | TFC binding to IFNA1 and IFNA2 promoter due TGF-β activation [48–50]. |
EEDc | Part of a transcription factor complex (TFC). | TFC binding to IFNA2 promoter [49, 50]. |
|
▼ miR-146b-5p | 0.57 | 0.78 | TRAF6, IRAK1 | NF-κB activation. | Increase proinflammatory cytokines (IL-1, IL-6, IL-8, TNF-α, and IL-12) [51]. |
STAT1, IRF5 | Hyperactivation of type I interferon pathway. | Increase type I IFN (a hallmark of SLE) [52]. |
|
▼ miR-142a-3p ▼ miR-142a-5p | 0.51 0.92 | 0.70a | SAP, CD84, & LL-10 | Increased SAP, CD84, and IL-10 protein levels. | CD4+ T cell overactivation and B cell hyperstimulation [53]. |
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▼ miR-342-3pb | −1.58 | 0.62 | EP300, BMPR2, & PDGFRA | NF-κB activation. Cytokine signaling. | Increase proinflammatory cytokines IL-1, IL-6, IL-8, and TNF-α (in type 1 diabetes mellitus) [14, 15]. (miRNA specifically decreased in SLE patients with active nephritis.) |
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▼ miR-200a-3p | 9.25 | 6.58 | SMAD2, GATA3, & FOXO3 | JAK/STAT, TGF-β, and mTOR pathways. | Induced differentiation of Th17 cells and inhibited Treg or T helper pathways (in multiple sclerosis) [36]. |
EED & EZH2c | Part of a transcription factor complex (TFC). | TFC binding to IFNA2 promoter [49, 50]. |
|
▲ miR-21a-5p | 1.16 | 1.65 | RASGRP1 & DNMT1 | Underexpression of DNA methyltransferase (DNMT1). | Hypomethylation of DNA. A possible key event in the pathogenesis of SLE [54, 55]. |
▲ miR-125a-5p | 2.90 | 1.34 | KLF13 | Reduction in the production of KLF13 and RANTES. | Reduction of the inflammatory chemokine RANTES levels [56]. |
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