Role of miR-146a in the Regulation of Inflammation in an In Vitro Model of Graves' Orbitopathy

Jang, Sun Young; Chae, Min Kyung; Lee, Joon‐Hyung; Lee, Mi Kyung; Yoon, Jin Sook

doi:10.1167/iovs.16-19213

Cited by 39 publications

(42 citation statements)

References 34 publications

(42 reference statements)

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“…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]. Besides, the overexpression of miR-146a could be induced by IL-10 and TGF-β but reduced by IL-12 and IFNα/β in hepatic carcinoma cells, which then led to the suppression of NK cell-mediated cytotoxicity and IFNγ/TNFα production [16].…”

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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“…In other studies, this polymorphism has been associated with an increase or decrease of susceptibility to different types of cancer such as colorectal cancer, 45 BC, 46 lung, 47 thyroid cancer 48 or inflammatory diseases. 49 In this study, we suggest that rs2910164SNP of miR-146a is associated to BC presentation. The C mutant allele and more particularly the CC genotype are associated to high grade, to age at diagnosis >50 years and to obesity.…”

Section: Discussionmentioning

confidence: 57%

Expression and polymorphism of micro-RNA according to body mass index and breast cancer presentation in Tunisian patients

Belaiba

Medimegh

Ammar

et al. 2018

Journal of Leukocyte Biology

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Micro-RNAs (miRs) constitute a class of small noncoding RNAs implicated in the regulation of gene expression by binding to target mRNAs. A miR can target several mRNAs, being involved in different biologic processes and pathologies. This pleiotropic function might explain the link between diseases co-occurrence. Epigenetic origin of the link between obesity and breast cancer (BC) is investigated in a cohort of Tunisian patients, focusing on polymorphism at germline level (miR-146a) and on expression in mammary tumors (miR-21, miR-146a, and miR-34a), according to body mass index (BMI) and clinico-pathologic features. The measure of miR expression in 60 mammary tumors was realized using quantitative RT-PCR. Study of rs 2910164 in miR-146a was performed by PCR and direct sequencing using blood DNA of 83 affected women and 50 unrelated subjects from Great Tunis. MiR-21, miR-146a, and miR-34a have been quantified in breast tumor according to BMI. MiR-21 is significantly more expressed in tumors of obese women comparatively to nonobese patients. On the contrary, miR-34a is decreased in tumors of obese women. Moreover, in obese BC patients, a significant increase in both miR-21 and miR-146a expression is revealed in cases with lymph node metastasis. The polymorphism at rs 2910164 (miR-146a) locus was not shown as a risk factor for BC. However the mutant CC genotype was revealed to be associated with a risk for bad outcome of the disease. Chronic inflammation in obese women would be linked to aggressive breast tumors via induction of oncomiRs overexpression and decrease of tumor suppressor miRs. K E Y W O R D Sbody mass index, mammary tumors, miR-146a, miR-21, miR-34a tions, transcription of these miRs is at baseline levels. In the context of inflammation, several stimuli such as cytokines (TNF-, IL-1 ) or ligands of TLR such LPS are capable of regulating the expression of these

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“…1 In addition to miR-146a, we also noted miR-155, another well-known micro-RNA in inflammatory autoimmune diseases. Both of them are immune-specific miRNAs and increasingly growing evidence indicates that miR-146a and miR-155 are both indispensable in the adaptive and the innate immune system.…”

mentioning

confidence: 64%

“…We have read with great interest the article published by Jang et al 1 We congratulate the authors for their study and their efforts to explore the potential role of miR-146a in the pathogenesis of Grave's orbitopathy (GO). The results in the article are displayed elegantly with convincing data.…”

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confidence: 99%