miRNA‐Regulated Key Components of Cytokine Signaling Pathways and Inflammation in Rheumatoid Arthritis

Sharma, Ashish Ranjan; Sharma, Garima; Lee, Sang-Soo; Chakraborty, Chiranjib

doi:10.1002/med.21384

Cited by 55 publications

(53 citation statements)

References 75 publications

(128 reference statements)

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“…MiR-146a, a member of the class of miRNAs, has been found to participate in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA), Osteoarthritis (OA), systemic lupus erythematosus (SLE), multiple sclerosis (MS) and GO [3, 9-13]. For instance, MiR-146a was reported to induce TNF-α production by targeting TNF-α/TNF receptor-associated factor 6 (TRAF6)/IL-1 receptor-associated kinase 1 (IRAK1) signaling in RA [14]. Again, miR-146a was reported to down-regulate IL-6 production in orbital fibroblasts [15].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of MicroRNA-146a/Notch2 Signaling Regulating IL-6 in Graves Ophthalmopathy

Wang

Chen

Long

2017

Cell Physiol Biochem

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Background/Aims: We intended to investigate the significance of microRNA-146a, Notch2 and IL-6 on Graves ophthalmopathy (GO) and the relationships among them. Methods: About 27 GO patients were incorporated in this study, including 13 patients with inactive GO and14 patients with active GO. Another 15 patients who had previously received strabismus orthopedics or ophthalmectomy due to trauma were selected as the control population. QRT-PCR assay was used to detect microRNA-146a and Notch2 expression levels in plasma. MTT assay and flow cytometry were respectively used to assess the viability and mitosis of the fibroblasts isolated from orbital connective tissue. Double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to detect serum IL-6 levels. The dual luciferase reporter gene assay was used to verify the targeting relationship between microRNA-146a and Notch2. Results: Compared with the control group, the relative expression of miR-146a was significantly increased whereas the relative expression of Notch2 was significantly decreased (all P < 0.05) in GO patients compare with the control. Notch2 can be directly targeted by microRNA-146a. The over-expression of miR-146a markedly facilitated Orbital Fibroblasts (OFs) viability and mitosis whereas markedly suppressed cell apoptosis (all P < 0.05). Exogenous microRNA-146a mimics could down-regulat the expression of Notch2 and up-regulate IL-6 (P < 0.05). The inhibition of microRNA-146 resulted in the elevated expression of Notch2 and decreased expression of IL-6 (P < 0.05). Conclusion: MicroRNA-146a may increase the IL-6 levels and exacerbate GO by directly targeting Notch2.

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Section: Introductionmentioning

confidence: 99%

Mechanism of MicroRNA-146a/Notch2 Signaling Regulating IL-6 in Graves Ophthalmopathy

Wang

Chen

Long

2017

Cell Physiol Biochem

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“…[19,20] On the other hand, miRNA- 146a is also able to regulate gene such FAF1, IRAK2, FADD, IRF-5, Stat-1, and PTC-1. [21] In arthritis mouse model, intravenous administration of double stranded miR-146a suppresses of cartilage and bone destruction. [20] These demonstrated that miR-146a may be involved in inflammatory responses in RA.…”

Section: Discussionmentioning

confidence: 99%

The role of circulating miR-146a in patients with rheumatoid arthritis treated by Tripterygium wilfordii Hook F

et al. 2017

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Rheumatoid arthritis (RA) is polygenic autoimmune disease with unclear etiology. MicroRNAs (miRNAs) play a critical role in the pathogenesis of RA. The objective of this study was to evaluate the role of miR-146a in patients with RA receiving Tripterygium wilfordii Hook F (TwHF) treatment.In total, 69 patients with RA and 69 healthy controls (HC) were included in the study, and patients with RA received TwHF treatment for 24 weeks. Blood samples were collected from RA patients and HC, and peripheral blood mononuclear cells (PBMCs) were isolated. Expression of miR-146a was analyzed in RA patients (baseline, 12 weeks and 24 weeks) and HC.Circulating miR-146a expression was markedly increased in patients with RA compared with healthy controls (P < .001), ROC analysis of miR-146a for diagnosis for RA showed that the AUC was 0.908 (95% CI: 0.862–0.955) with a sensitivity of 87.0% and a specificity of 82.6% at best cutoff. And miR-146a expression was positively associated with the DAS28 score and CRP level (P = .002 and P = .019). Moreover, miR-146a expression was markedly reduced after TwHF therapy (P < .001), and baseline miR-146a level was observed to present an increased tendency in responders compared with non-responders at 24 weeks (P = .066).Our study presented that circulating miR-146a level was correlated with risk and disease activity of RA patients by TwHF treatment, which could strikingly decrease expression of miR-146a in RA patients, and miR-146a may have a value in predicting clinical response of TwHF treatment. It indicates that circulating miR-146a plays a prominent role in RA patients treated by TwHF.

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“…[5][6][7][8] Accumulating evidences have proven that several miRNAs have established their value on the progress of various immune diseases, including RA, systemic lupus erythematosus (SLE), and psoriasis, which uncovered the potential of miRNA as marker for RA progression and prognosis. [9][10][11][12][13][14][15] However, no studies investigate the effect of comprehensive miRNA expression profile on predicting clinical response to TNF inhibitor in RA patients. Thus, in the present study, the aim was to explore the correlation of circulating miRNA expression profile with clinical response to TNF inhibitor in treating active RA patients.…”

Section: Introductionmentioning

confidence: 99%

Correlation of microRNA expression profile with clinical response to tumor necrosis factor inhibitor in treating rheumatoid arthritis patients: A prospective cohort study

Liu

Han

et al. 2019

Clinical Laboratory Analysis

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This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: This study aimed to explore the correlation of circulating microRNA (miRNA) expression profile with clinical response to tumor necrosis factor (TNF) inhibitor in treating rheumatoid arthritis (RA) patients. Methods: Baseline PBMC samples from eight responders and eight non-responders after 24-week TNF inhibitor (etanercept) treatment were subjected to miRNA microarray. Then, top 10 dysregulated miRNAs were selected and further validated by quantitative polymerase chain reaction (qPCR) in baseline PBMC samples from 92 RA patients treated with 24-week TNF inhibitor (etanercept). Responders and nonresponders were divided referring to the decline in disease activity score in 28 joints.Results: In microarray assay, total 59 upregulated and 78 downregulated miRNAs were identified in responders compared to non-responders, which were mainly enriched in regulating immune-and inflammation-related biological processes and pathways. The top 10 dysregulated miRNAs were as follows: miR-192-5p, miR-146a-5p, miR-19b-3p, miR-320c, miR-335-5p, miR-149-3p, miR-766-3p, let-7a-5p, miR-24-3p, and miR-1226-5p. In qPCR validation, miR-146a-5p was increased, while let-7a-5p was decreased in responders compared with non-responders. Multivariate logistic analysis illuminated that miR-146a-5p and CRP independently correlated with higher clinical response, while let-7a-5p and biologics history independently associated with lower clinical response. Subsequently, receiver operating characteristic curve showed that combination of these four independent factors presented with a great predictive value for clinical response with area under curve: 0.863, 95% CI 0.781-0.945.Conclusion: miRNA expression profile is closely implicated in the treatment efficacy of TNF inhibitor, and combined measurement of miR-146a-5p, let-7a-5p, CRP, and biologics history disclosed a great predictive value for clinical response to TNF inhibitor in RA patients. How to cite this article: Liu Y, Han Y, Qu H, Fang J, Ye M, Yin W. Correlation of microRNA expression profile with clinical response to tumor necrosis factor inhibitor in treating rheumatoid arthritis patients: A prospective cohort study.

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miRNA‐Regulated Key Components of Cytokine Signaling Pathways and Inflammation in Rheumatoid Arthritis

Cited by 55 publications

References 75 publications

Mechanism of MicroRNA-146a/Notch2 Signaling Regulating IL-6 in Graves Ophthalmopathy

Mechanism of MicroRNA-146a/Notch2 Signaling Regulating IL-6 in Graves Ophthalmopathy

The role of circulating miR-146a in patients with rheumatoid arthritis treated by Tripterygium wilfordii Hook F

Correlation of microRNA expression profile with clinical response to tumor necrosis factor inhibitor in treating rheumatoid arthritis patients: A prospective cohort study

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