MiR-146a-5p May Target TRAF6 And IRAK1 To Participate In The Development Of Hashimoto’s Thyroiditis

Background and Purpose: Micrornas are small single-stranded noncoding RNAs,consisting of approximately 22(20-24)nucleotides,that inhibit gene expression by selectively binding to the 3’ untranslated region(3’-UTR)of messenger RNA(m RNA)in a base-complementing pairing mode.Hashimoto’s thyroiditis(HT)is an autoimmune thyroid disease characterized by massive replacement of thyroid tissue with lymphocytes,increased serum autoantibodies,and destruction of thyroid follicular cells,ultimately leading to hypothyroidism.The majority of female patients,early manifestations are asymptomatic or palpitations,fear of heat,hyperhidrosis and other related symptoms of hyperthyroidism,later can be further developed lethargy,fatigue,apathetic expression and other related manifestations of hypothyroidism.At present,the pathogenesis of Hashimoto’s thyroiditis is mainly believed to be caused by the imbalance of Th1/Th2 cell differentiation,and it is also believed to be related to Th17 cell differentiation,but the specific mechanism remains unclear.MiR-146a-5p is known to be closely related to autoimmune diseases and also plays an important role in inflammation,tumor development and bone marrow cell proliferation.Therefore,this study mainly discusses the possible role and mechanism of miR-146a-5p in the occurrence and development of Hashimoto’s thyroiditis.Methods: Thyroid tissues of patients undergoing thyroidectomy with HT and normal thyroid tissues without lesion involvement were collected from April 2021 to August 2021 in The Affiliated Hospital of Southwest Medical University.HT tissue is a serologic indicator of preoperative thyroid function,indicating a significant increase in anti-thyroglobulin antibody(Tg Ab)or anti-thyroperoxidase antibody(TPOAb),and thyroid tissue with enlarged thyroid volume and abundant blood supply during operation.The thyroid tissues not involved in the lesions were normal thyroid tissues with normal intraoperative thyroid volume and normal thyroid tissues confirmed as HT tissues and normal thyroid tissues by HE staining.The expression level of miR-146a-5p in HT tissues was detected by Real time fluorescence quantitative PCR(RT-QPCR).Meanwhile,the expression of miR-146a-5p was simulated and knocked down by cell transfection test to further clarify the possible role of miR-146a-5p in the development and progression of HT.Western blot(WB)was used to detect the expression levels of related proteins.Results: MiR-146a-5p was highly expressed in HT tissues(P<0.01).Western blot results of thyroid tissue showed that IL-1 receptorassociated kinase1(IRAK1),TNF receptor-associated Factor 6(TRAF6),expression decreased(P<0.05 P<0.01);Down-regulated the expression of IRAK1 and TRAF6 was observed by up-regulating miR-146a-5p in Jurkat T cells(P<0.01,P<0.001),and increased the expression of IRAK1 and TRAF6 was observed after down-regulation of miR-146a-5p(P<0.001).The level of miR-146a-5p was negatively correlated with the activation of Nuclear factor-Kappa B(NF-κB)and the secretion of downstream inflammatory factor IL6.Conclusions: MiR-146a-5p negatively regulates NF-κB pathway by targeting IRAK1 and TRAF6,and reduces the production of inflammatory factors such as IL6,thus participating in the regulation of HT development.