Table 5.
List of miRNAs whose expression has been upregulated in SLE patients (LPS: lipopolysaccharide, DC: dendritic cell, NK: natural killer).
| miRNA | Number of Clinical Samples | Assessed Cell Line | Targets/Regulators | Signaling Pathways | Function and Comments | Reference |
|---|---|---|---|---|---|---|
| miR-663 | A total of 13 SLE patients and 10 healthy controls were enrolled. | BM-MSCs | TGF-β1, JUNB and JUND, MYL9, GRID2D, EPHB3 | P38/MAPK and Akt signaling pathways | The inhibition of miR-663 in BMSCs could restore the production of Treg and Tfh cells through the secretion of TGF-β1. | [54] |
| miR-155 | 24 SLE patients and 75 healthy donors were enrolled. | Serum | SHIP1, SOCS1, EKKε, TAB2, S1pr1, IL4, IL-17A | U1-RNP/TLRs/IFNs signaling pathway | MiR-155 regulates the distribution of T cells. | [55] |
| miR-143 | TLR2, NFκB | MiR-143 reduces the production of TLR4 and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). | ||||
| miR-132 | IRAK4 | Monocytes and macrophages show an increased expression of miR-132 in response to LPS. | ||||
| miR-126 | TRAF6, IFN | MiR-126 inhibits the release of proinflammatory cytokines. | ||||
| miR-29a | IFN-γ | MiR-29a contributes to inhibiting the response to intracellular bacterial infections. | ||||
| miR-448 | 27 SLE patients and 34 healthy controls were recruited in this study. | Serum | TNF, TGF-β, NF-κB and MAPK signaling pathways | These miRNAs may have regulatory effects on immunity by affecting signaling pathways, and may represent specific biomarkers for distinguishing patients with autoimmune diseases from healthy controls. | [48] | |
| miR-551b | ||||||
| miR-130b-3p | 60 SLE patients suffering from LN and 30 healthy controls were recruited. | Serum | ERBB2IP, PGC-1α, PPAR-γ | TGF-β-induced signaling pathways | The circulating miR-130b-3p might serve as a biomarker and play an important role in renal damage in early-stage LN patients. | [56] |
| miRNA-371b | Samples were collected from 1092 SLE patients and 553 healthy controls. | Serum | It was suggested that the microRNAs mentioned may be associated with aberrant functions of CD4+ and CD8+ T cells in SLE. | [57] | ||
| miRNA-5100 | ||||||
| hsa-miR-30e-5p | 70 SLE patients and 40 healthy controls were included. | Plasma | Granzyme B, perforin | MiR-30e expression is suppressed by IFN-α, which in turn suppresses natural killer cell cytotoxicity by targeting granzyme B and perforin. | [58] | |
| miR-142-3p | 68 SLE patients and 68 healthy controls were enrolled. | Plasma | TGFBR1 | TGFβ signaling pathway | Increased miR-142-3p expression may be caused by increased cellular release of this miRNA through increased exocytosis and/or the normal exocytosis of cells containing increased miRNA. | [45] |
| miR-181a | This miRNA is important for hematopoietic cell differentiation, increases the fraction of B-lineage cells, and is also expressed by endothelial cells. | |||||
| miR-132 | Human THP-1, HEK293, and murine RAW264.7 cells were obtained from the American Type Culture Collection. | PBMCs | IRAK4 | TLR-signaling pathway | MiR-132 was shown to regulate neuronal morphogenesis and the dendritic plasticity of cultured neurons. | [59] |
| miR-212 | MiR-212 can interfere with the craving for cocaine in mice and acts as a tumor suppressor. | |||||
| miR-25 | 28 SLE patients and 28 healthy controls were enrolled in this study. | PBMCs | AMPD2 | Purine biosynthesis and metabolism | This study suggested that mentioned miRNAs represent novel diagnostic biomarkers, disease activity markers and potential therapeutic targets for SLE. | [60] |
| miR-1273h-5p | Genes encoding peroxidase, glycosyltransferase, ATP synthase and hydrolase, carbohydrate phosphatase and exoribonuclease | |||||
| miR-148a | 8 SLE patients and 7 healthy controls were enrolled in this study. | PBMCs | Gadd45α, PTEN, Bim, DNMT, Bcl2l11 | DNA methylation pathway | Members of the miR-148 family, including miR-148a, miR-148b and miR-152, are negative regulators of the innate response and Ag-presenting capacity of DCs. | [33,61] |
| miR-152 | ||||||
| miR-224 | STAT-1, API5 | Enhanced expression of miR-224 accelerates T cell activation-induced cell death. | ||||
| miR-326 | ||||||
| hsa-miR-345 | 99 SLE patients and 65 healthy controls were enrolled. | PBMCs | IRF8 | IRF8 is a transcription factor which has a key role in regulating the differentiation of B cells and promoting their differentiation. It is revealed that IRF8 is inhibited by hsa-miR-345. | [62] | |
| miR-16 | 30 SLE patients and 20 healthy controls were enrolled in this study. | PBMCs | MAPK pathway | It was proposed that the over-expression of miR-16 in the blood may be associated with the exposure of immune and inflammatory cells to the circulating blood. | [63] | |
| miR-451 | Higher circulating levels of miR-451 might be associated with abnormal erythropoiesis. | |||||
| miR-21 | MRL/lpr mice and control MRL/MpJ mice were purchased from the Jackson Laboratory (JAX, Maine, USA) | PBMCs | DNMT1 | MiR-21 is highly expressed in CD41 T cells in patients with SLE and may contribute to DNA hypomethylation in lupus CD41 T cells. | [33,64] | |
| miR-127 | ||||||
| miR-182 | ||||||
| miR-27a | Samples from 37 SLE patients and 17 healthy controls were collected. | PBMC/NK cells | NKG2D | This study highlighted the expression profile of miR-27a and its potential target NKG2D which is of prime importance for NK cell activation in SLE. |
[65] | |
| miR-30a | B cells | Lyn | Pathways of B cell activation | A high level of miR-30a might be responsible for the development of B cell hyperactivity, suggesting that it could be involved in the pathogenesis of SLE. | [66] | |
| miR-152-3p | 30 SLE patients and 30 healthy controls were recruited. | B cells | BAFF, KLF5 | Knockdown of miR-152-3p expression inhibits the self-reactivity of SLE B cells, thereby reducing their autoantibody production. | [67] | |
| miR-29b | 36 SLE patients and 28 healthy donors were recruited in this study. | T cells | sp1, DNMT1 | MiR-29b reduces DNMT1 expression levels, thereby resulting in DNA hypomethylation and the over-expression of methylation-sensitive genes, and mediates the pathogenesis of SLE. | [38] | |
| miR-451a | Wild-type (WT, n = 10), Faslpr/lpr (n = 10), and miR-451a−/− Faslpr/lpr (n = 10) female C57B/L6 mice were recruited. | Spleen and thymus tissues | IRF8 | IFN pathway | The knockout of miR-451a affects the enlargement of the spleen and reduces urine protein content and immune complex deposits. | [68] |
| miR-150 | Formalin-fixed paraffin-embedded kidney specimens from 14 SLE patients suffering from LN and from 2 normal controls were gathered. | Kidney biopsy | SOCS1 | Janus kinase/signal transducers | The over-expression or TGF-β1-induced increase of miR-150 directly decreases SOCS1, leading to increases in profibrotic protein production. | [69] |
| let-7 family | Samples were collected from 98 SLE patients and 47 healthy controls. | Kidney biopsy | TNFAIP3 | Let-7-TNFAIP3-NF-κB pathway | The over-expression of let-7 miRNAs leads to the increased phosphorylation and sustained degradation of IκBα and the enhanced phosphorylation of p65. | [70] |