ERα通过调控circ-EIF4G3/miR-374b-5p/ANXA1通路在结节性硬化症进展中的机制研究

结节性硬化症（TSC）是常染色体显性遗传病，肾脏病变常见。女性患者疾病进展快，预后差，部分妊娠期疾病快速进展。雌激素受体α（ERα）在TSC患者肾脏病变中特异表达。外源性雌二醇和过表达ERα能促进细胞增殖，氟维司群和敲低ERα抑制增殖。因此，TSC进展受性激素调控，ERα发挥重要作用。预实验发现，ERα通过调控ANXA1表达促进TSC细胞增殖，但ERα不能直接作用于ANXA1的启动子。ERα可通过下调环状RNA circ-EIF4G3抑制ANXA1表达，生物信息学分析显示circ-EIF4G3序列中存在miR-374b-5p结合位点，而miR-374b-5p可直接作用于靶基因ANXA1。我们推测，ERα通过下调circ-EIF4G3，进而通过miR-374b-5p/ANXA1通路促进TSC细胞增殖。本项目将对ERα在TSC进展中作用和机制进行研究，为TSC患者个体化治疗提供理论基础和依据。

Tuberous sclerosis complex (TSC) is an autosomal dominant inherited disease in which renal lesions are common. The disease progresses quickly in female patients with poor prognosis, and the disease progresses rapidly in some pregnancies. Estrogen receptor α (ERα) expression is specific in TSC renal masses. Exogenous estradiol and overexpression of ERα promoted cell proliferation, while faslodex and knockdown ERα inhibited cell proliferation. Therefore, the progression of TSC is regulated by sex hormones and ERα plays an important role. Preliminary experiments showed that ERα promoted TSC cell proliferation by regulating the expression of ANXA1, but ERα could not directly act on the promoter of ANXA1. ERα inhibited the expression of ANXA1 by down-regulating circRNA circ-EIF4G3. Bioinformatics analysis showed that the circ-EIF4G3 sequence contained miR-374b-5p binding site, and miR-374b-5p could directly act on the target gene ANXA1. We speculated that ERα promoted TSC cell proliferation through the down-regulation of circ-EIF4G3, and through the miR-374b-5p/ANXA1 pathway. This project will study the role and mechanism of ERα in the progression of TSC, and provide theoretical basis and basis for individualized treatment of TSC patients.