Abstract：
Interleukin-17A (IL-17A) plays a pivotal role in the pathogenesis of Graves\' disease (GD), an autoimmune disorder affecting thyroid function, but the detailed regulatory mechanisms remain elusive. Circular RNAs (circRNAs) have emerged as key regulators of IL-17A expression and secretion in autoimmune diseases, yet their specific role in GD, especially within CD4 + T lymphocytes, are not well understood. In this study, a circRNA, circPHF16 (hsa_circ_0090364) was found to be highly expressed in the peripheral blood mononuclear cells and serum of GD patients. In vitro experiments in Jurkat T cells revealed that silencing of circPHF16 suppressed IL-17A expression and secretion, while overexpression of circPHF16 had the opposite effect. Furthermore, bioinformatics analysis demonstrated a circPHF16/miR-378a-3p/IL6ST pathway, in which circPHF16 regulates IL6ST expression, which, in turn, influences IL-17A expression and secretion by interacting with miR-378a-3p. In vivo studies in a mouse model of GD showed similar trends in molecular expression levels, consistent with competitive endogenous RNA interactions. Together the results of the study identify circPHF16 as a potential target in the development of new strategies for GD diagnosis and treatment, and thus, offer a theoretical foundation for clinical therapeutic approaches in GD.
摘要：
白细胞介素-17A（IL-17A）在Graves病（GD）的发病机制中起关键作用，一种影响甲状腺功能的自身免疫性疾病，但是详细的监管机制仍然难以捉摸。环状RNA（circularRNAs，circRNAs）已经成为自身免疫性疾病中IL-17A表达和分泌的关键调节因子，然而它们在GD中的特定作用，特别是在CD4+T淋巴细胞内，不是很了解。在这项研究中,一个circRNA，发现circPHF16(hsa_circ_0090364)在GD患者外周血单核细胞和血清中高表达。在JurkatT细胞的体外实验表明，沉默circPHF16抑制IL-17A的表达和分泌，而circPHF16的过表达具有相反的作用。此外，生物信息学分析显示circPHF16/miR-378a-3p/IL6ST通路，其中circPHF16调节IL6ST表达，which,反过来,通过与miR-378a-3p相互作用影响IL-17A的表达和分泌。GD小鼠模型的体内研究显示分子表达水平的相似趋势，与竞争性内源性RNA相互作用一致。该研究的结果共同确定了circPHF16作为GD诊断和治疗新策略开发的潜在目标，因此，为GD的临床治疗提供理论基础。
