内质网应激介导的内源性竞争LINC00842与miR-214在胺碘酮致桥本氏甲状腺炎中的功能及作用机制

Hashimoto’s thyroiditis（HT）is a common sort of autoimmune thyroid disease（AITD）. In clinical, the incidence rate of HT in persons taking amiodarone is significant higher than others. However, the mechanism of this phenomenon is still unclear. In our pilot experiments, the expression of XBP1s (a endoplasmic reticulum stress-related protein) in HT patients with long-term use of amiodarone is higher than its in HT patients without taking amiodarone or iodic medicines. Base on these results, we tend to focus on the mechanism of amiodarone-induced HT via the XBP1s ERS pathway and the competing endogenous RNAs (LINC00842 and miR-214). The implementation of present program could support the further theoretical basis for the onset of HT, and could also provide the novel therapy strategy for intervention and treatment of the clinical side effect of amiodarone.

桥本氏甲状腺炎（HT），是常见的自身免疫甲状腺炎（AITD）。临床上长期服用胺碘酮的人群发生HT的几率远高于其他人群，然而其机制尚不清楚。我们的预实验发现，长期服用胺碘酮的HT病人中，其甲状腺滤泡上皮细胞中内质网应激相关蛋白XBP1s表达量显著高于非胺碘酮/典类药物服用病人，同时伴随着LINC00842表达增高、miR-214表达降低及FASL表达升高。在此基础上，本课题拟以XBP1s内质网应激为切入点，通过体内外实验，结合LINC00842与miR-214的ceRNA调控作用，探讨胺碘酮诱发HT的相关机制，为进一步阐释HT的发病机理及为临床上胺碘酮副作用的干预与治疗提供新的理论依据及策略。

桥本甲状腺炎(HT)是一种特异性自身免疫性疾病，最终导致甲状腺功能减退。XBP1是一种内质网应激相关蛋白，参与多种疾病的发病机制。在本研究中，胺碘酮加重了HT患者和甲状腺滤泡上皮细胞的内质网应激反应。研究结果显示，miR-214在胺碘酮治疗的甲状腺炎患者的组织中低表达。MiR-214可提高胺碘酮诱导的甲状腺滤泡上皮细胞的存活率，抑制细胞凋亡。XBP1基因的下调可抑制胺碘诱导的甲状腺滤泡上皮细胞凋亡。XBP1通过与LINC00842启动子结合，增强了HT患者和甲状腺滤泡上皮细胞LINC00842的表达。LINC00842在HT患者甲状腺滤泡上皮细胞中作为miR-214的海绵吸附作用。LINC00842通过抑制miR-214上调Fas配体(FASL)的表达。过表达FASL逆转了胺碘处理后shXBP1诱导的甲状腺滤泡上皮细胞凋亡的抑制。结果表明，胺碘酮驱动的XBP1通过调节LINC00842/miR-214/FASL轴，加重了HT的内质网应激和凋亡，为胺碘酮诱导的HT的治疗策略提供了新的视角。