Table 4.
List of miRNAs whose expression has been downregulated in SLE patients.
| miRNA | Number of Clinical Samples | Assessed Cell Line | Targets/Regulators | Signaling Pathways | Function and Comments | Reference |
|---|---|---|---|---|---|---|
| miR let-7f | In total 15 SLE patients and 10 normal controls were enrolled. | Bone marrow-derived mesenchymal stem cells (BM-MSCs)/PBMCs | IL-6 | STAT3 signaling pathway | MiR let-7f increases the apoptosis rate of BM-MSCs through targeting IL-6 and activating the STAT3 pathway. | [39] |
| miR-31 | MRL/lpr mice and control MRL/MpJ mice were purchased from the Jackson Laboratory (JAX, Maine, USA) | PBMCs | Foxp3, serine/threonine kinase 40, IL-2 | NF-κB signaling pathway | MiR-31 enhances inflammatory cytokine production. | [33] |
| miR-98 | Samples from 41 SLE patients and 20 healthy controls were collected. | PBMCs | IL-6 | IL-6/STAT3 signaling pathway | MiR-98 could ameliorate STAT3-mediated cell proliferation and inflammatory cytokine production. | [40] |
| Samples from 48 SLE patients and 39 healthy controls were collected. | PBMCs | Fas | Fas-mediated apoptosis | MiR-98 downregulation contributes to the dysregulation of apoptosis in SLE. | [41] | |
| miR-125a | Samples were gathered from 10 SLE patients and 8 healthy donors. | PBMCs | KLF13, RANTES | Inflammatory chemokine pathway | MiR-125a acts as a negative regulator in the feedback loop of RANTES expression in activated T cells. | [42] |
| miR-125b | 50 SLE patients and 26 healthy controls were enrolled in this study. | PBMCs | TNF-α, ETS1, STAT3 | NF-κB signaling | MiR-125b expression correlates with LN and the dysfunction of T cells by affecting the target genes ETS1 and STAT3. |
[43] |
| miR-302d | PBMCs | IRF9 | IFN pathway | Inhibition of the type I IFN pathway through the manipulation of miR-302d levels could be beneficial in SLE patients who present with clinical disease driven by IFN dysregulation. | [44] | |
| miR-106a | 68 SLE patients and 68 healthy controls were enrolled. | Plasma | CREB1, TGFBR2 | TGFβ signaling pathway | These control monocytopoiesis and regulate regulatory T cells. | [45] |
| miR-20a | ||||||
| miR-17 | Bim, PTEN, CREB1, TGFBR2 | These regulate apoptosis, control monocytopoiesis and regulate regulatory T cells. | ||||
| miR-20a | ||||||
| miR-92a | ||||||
| miR-203 | TGFBR1/2, ACVR2A/2B, SMAD6/7, SMURF1, BMPR2, MAPK1 | This miRNA targets genes in the MAPK signaling and cytokine–cytokine receptor pathways and many genes involved in focal adhesion and tight junctions. | ||||
| miR-342-3p | The association of miR-223 and miR-342-3p with lupus nephritis was observed in this study. | |||||
| miR-223 | ||||||
| miR-200b-5p | 101 SLE patients suffering from LN and 100 healthy controls were enrolled. | Plasma | IKBKB, IL-8, IL-6, NF-kB | Type I IFN, PTEN, KLK4 and SOCS1 | The miR-200 family could target several genes and pathways to inhibit inflammatory responses and kidney fibrosis, thereby decreasing renal damage. | [46] |
| miR-200c-5p | ||||||
| miR-141-5p | ||||||
| miR-103 | 50 SLE patients and 30 healthy controls were involved in this study. | Plasma | The signature of circulating miRNAs will provide novel biomarkers for the diagnosis of SLE and the evaluation of disease activity and LN. | [34] | ||
| miR-15b | ||||||
| miR-19b | ||||||
| miR-22 | ||||||
| miR-23a | ||||||
| miR-93 | ||||||
| miR-654 | Samples from 24 SLE patients and 24 controls were collected. | Serum | ERK, AKT, IL-1β, IL-6, IL-8, TNF-α | MIF-dependent pathways | MiR-654 inhibits MIF (migration inhibitory factor) expression via binding to MIF 3’ UTR and reduces downstream inflammatory cytokine production. | [47] |
| miR-124 | 27 SLE patients and 34 healthy controls were recruited in this study. | Serum | TNF, TGF-β, NF-κB and MAPK signaling pathways | This miRNA may have regulatory effects on immunity by affecting signaling pathways, and may represent a specific biomarker for distinguishing patients with autoimmune diseases from healthy controls. | [48] | |
| miR-146a | 52 SLE patients and 29 healthy controls were recruited. | Serum | IRAK1, TRAF6, IRF-5, STAT-1 | Type I IFN pathway | The under-expression of miR-146a in lupus patients is relevant to the biological and clinical behavior of SLE. | [49] |
| miR-1246 | A total of 50 SLE patients and 20 healthy controls were enrolled. | B cells | EBF1 | AKT-P53 signaling pathway | Therapies that turn the expression of affected miR-1246 genes back to normal could serve as a potential and effective method for treating SLE. | [50] |
| miR-377 | 42 SLE patients and 48 healthy controls contributed to the study. | T cells | Vitamin D signaling pathway | Severe vitamin D deficiency is associated with decreased observed miRNA levels in SLE patients. VDR mRNA expressions in the T cells of SLE patients were significantly lower than those in controls, but CYP24A1 and CYP27B1 mRNA levels were significantly increased. | [51] | |
| miR-342 | ||||||
| miR-10a | ||||||
| miR-374b | ||||||
| miR-410 | ||||||
| miR-410 | 20 SLE patients and 20 healthy subjects were recruited. | T cells | STAT3 | STAT3 signaling pathway | MiR-410 is the key regulatory factor in the pathogenesis of SLE, which regulates the expression of IL-10. | [37] |
| miR-145 | Samples from 26 SLE patients and 27 healthy controls were collected. | T cells | STAT1 | Interferon-mediated signaling pathway | The over-expression of miR-145 suppresses the gene expression of STAT-1 which seems to be associated with lupus nephritis. | [36] |
| miR-23b | 18 SLE patients suffering from LN and 9 healthy controls were enrolled. | Kidney biopsy | TAB2, TAB3, IKK-α | NF-κB pathway | The over-expression of miR-23b suppresses both TNF-α- and IL-1β-induced NF-κB activation. | [52] |
| hsa-miR-371-5p | 35 SLE patients suffering from LN and 35 healthy controls were included in this study. | Kidney biopsy | HIF-1α | The over-expression of hsa-miR-371-5p may inhibit mesangial cell proliferation and promote apoptosis. | [53] |