Expression and Clinical Significance of miR-146a and Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) in Myasthenia Gravis Patient Serum

Yan, Mei; Fu, Yue; Rao, Hui Lan; Zhou, Huiling; Liang, Xiaohuang

doi:10.1155/2021/5573469

Cited by 8 publications

(5 citation statements)

References 12 publications

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“…The miRNA plays a key role in the regulation of the pathogenesis of MG. miRNA is considered to be related to the immune regulation activation mechanism, especially related to the process of T cell response, inflammatory response, and the expression of inflammatory factors. The related research of MG-specific miRNA can provide value for its pathogenesis and treatment [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

miR-181a Ameliorates the Progression of Myasthenia Gravis by Regulating TRIM9

Wang

Liu

Kuang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Abnormally activated CD4+ T cells are considered to be an important factor in the pathogenesis of myasthenia gravis (MG). In the pathogenesis of MG, the imbalance of proinflammatory cytokines and immune cells maintains the imbalance of immune response and inflammatory microenvironment. Studies have shown that miRNA is involved in the pathogenesis of MG. In our experiment, we extracted peripheral blood mononuclear cells (PBMCs) from MG patients and detected the expression of miR-181a and TRIM9 in PBMCs by qRT-PCR. In vitro experiments were conducted to explore the regulatory mechanism of miR-181a on target genes and its influence on inflammatory factors related to MG disease. Experimental autoimmune myasthenia gravis (EAMG) model mice are established, and the effects of miR-181a on EAMG symptoms and inflammatory factors are explored through in vivo experiments. According to a total of 40 EAMG mice that were successfully modeled, all EAMG mice showed symptoms of muscle weakness; their diet was reduced; their weight gain was slow; and even weight loss occurred. In MG patients and EAMG mice, the expression of miR-181a was low and TRIM9 was highly expressed. Bioinformatics website and dual-luciferase report analysis of miR-181a had a targeting relationship with TRIM9, and miR-181a could target the expression of TRIM9. After upregulating miR-181a or interfering with TRIM9, serum miR-181a in EAMG mice was significantly upregulated; TRIM9 was significantly downregulated; its clinical symptoms were reduced; and the expression of inflammatory factors was reduced. The study finally learned that miR-181a can reduce the level of MG inflammatory factors by targeting the expression of TRIM9 and has the effect of improving the symptoms of MG.

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Section: Introductionmentioning

confidence: 99%

miR-181a Ameliorates the Progression of Myasthenia Gravis by Regulating TRIM9

Wang

Liu

Kuang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Intriguingly, Yan et al. ( 60 ) proposed that overexpressed miR-146a may contribute to the pathogenesis of MG by promoting TRAF6 expression, which could further disrupt Treg function. miR-125a-5p was confirmed to negatively regulate Foxp3, consequently inhibiting the generation of Treg with a great possibility ( 37 ).…”

Section: Mirnas In Mgmentioning

confidence: 99%

“…Recent research outcomes have unveiled a miR-146b-TRAF6-NF-kB-Foxp3 pathway, which plays a crucial role in suppressing Treg proliferation and its inhibitory function (49, 59). Intriguingly, Yan et al (60) proposed that overexpressed miR-146a may contribute to the pathogenesis of MG by promoting TRAF6 expression, which could further disrupt Treg function. miR-125a-…”

Section: Modulation Of Tregs Th17 and Th1mentioning

confidence: 99%

The intricate dance of non-coding RNAs in myasthenia gravis pathogenesis and treatment

Wang,

Zhu,

Liu

et al. 2024

Front. Immunol.

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Myasthenia gravis (MG) stands as a perplexing autoimmune disorder affecting the neuromuscular junction, driven by a multitude of antibodies targeting postsynaptic elements. However, the mystery of MG pathogenesis has yet to be completely uncovered, and its heterogeneity also challenges diagnosis and treatment. Growing evidence shows the differential expression of non-coding RNAs (ncRNAs) in MG has played an essential role in the development of MG in recent years. Remarkably, these aberrantly expressed ncRNAs exhibit distinct profiles within diverse clinical subgroups and among patients harboring various antibody types. Furthermore, they have been implicated in orchestrating the production of inflammatory cytokines, perturbing the equilibrium of T helper 1 cells (Th1), T helper 17 cells (Th17), and regulatory T cells (Tregs), and inciting B cells to generate antibodies. Studies have elucidated that certain ncRNAs mirror the clinical severity of MG, while others may hold therapeutic significance, showcasing a propensity to return to normal levels following appropriate treatments or potentially foretelling the responsiveness to immunosuppressive therapies. Notably, the intricate interplay among these ncRNAs does not follow a linear trajectory but rather assembles into a complex network, with competing endogenous RNA (ceRNA) emerging as a prominent hub in some cases. This comprehensive review consolidates the landscape of dysregulated ncRNAs in MG, briefly delineating their pivotal role in MG pathogenesis. Furthermore, it explores their promise as prospective biomarkers, aiding in the elucidation of disease subtypes, assessment of disease severity, monitoring therapeutic responses, and as novel therapeutic targets.

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“…Recently, TRAF6 expression was found to be upregulated in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), hyperplastic thymuses and MG patient serum. Studies have demonstrated that miR-146a and TRAF6 exhibit high mRNA expression in peripheral blood mononuclear cells (PBMCs) in MG patients [8,[10][11][12]. In addition, the relationships between TRAF6 expression in peripheral blood B cells and the clinical characteristics of MG patients have rarely been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Expression of TRAF6 in peripheral blood B cells of patients with myasthenia gravis

et al. 2022

BMC Neurol

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Background Tumor necrosis factor receptor-associated factor 6 (TRAF6) can regulate the activation of inflammatory signaling pathways by acting as an E3 ubiquitin ligase, which enhances B cell activation. This study aimed to evaluate the expression of TRAF6 in the peripheral blood B cells of myasthenia gravis (MG) patients and analyze the relationships between TRAF6 expression and clinical characteristics. Method In our study, the expression level of TRAF6 in peripheral blood B cells of 89 patients was measured by flow cytometry compared with that of healthy subjects. The effects of disease severity, MG classification and immunotherapy on TRAF6 expression level were also analyzed. Results In our study, TRAF6 expression was elevated in CD19+ B cells and CD19+CD27+ memory B cells in generalized MG (GMG) patients compared with ocular MG (OMG) patients (p = 0.03 and p = 0.03, respectively). There was a significant positive correlation between the TRAF6 expression level and disease severity in both OMG patients and GMG patients (CD19+ B cells: OMG: p < 0.001, r = 0.89; GMG: p = 0.001, r = 0.59; CD29+CD27+ B cells: OMG: p = 0.001, r = 0.80; GMG: p = 0.048, r = 0.38). TRAF6 expression was significantly elevated in CD19+ B cells and CD19+CD27+ memory B cells in GMG with acute aggravation compared with GMG in MMS (p = 0.009 and p = 0.028, respectively). In the eleven MG patients who were followed, TRAF6 expression in B cells and memory B cells was significantly decreased after treatment (p = 0.03 and p < 0.01, respectively). Conclusion TRAF6 is potentially a useful biomarker of inflammation in patients with MG, and might be used to evaluate the effectiveness of treatment.

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Expression and Clinical Significance of miR-146a and Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) in Myasthenia Gravis Patient Serum

Cited by 8 publications

References 12 publications

miR-181a Ameliorates the Progression of Myasthenia Gravis by Regulating TRIM9

miR-181a Ameliorates the Progression of Myasthenia Gravis by Regulating TRIM9

The intricate dance of non-coding RNAs in myasthenia gravis pathogenesis and treatment

Expression of TRAF6 in peripheral blood B cells of patients with myasthenia gravis

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