环状RNA-RAB11FIP1通过竞争性抑制miR-129影响上皮性卵巢癌自噬及铁死亡的机制研究

上皮性卵巢癌是一类严重威胁女性健康的疾病，其病因及发病机制尚不明确。我们前期的研究发现环状RNA能通过调控细胞自噬影响上皮性卵巢癌的恶性进展。故在本项目中，我们通过激活上皮性卵巢癌的细胞自噬，并使用高通量测序技术和生物信息学分析发现，环状RNA-RAB11FIP1可能是该病重要的靶点。进一步研究证实，环状RNA-RAB11FIP1在上皮性卵巢癌组织中高表达并能促进细胞自噬，该基因还能与miR-129相互结合，可能影响ATG7与GPX4的表达。故推测：环状RNA-RAB11FIP1可能通过竞争性抑制miR-129，调控ATG7而促进上皮性卵巢癌自噬，同时影响GPX4的表达，协同抑制铁死亡。本课题拟通过建立沉默和过表达环状RNA-RAB11FIP1的卵巢癌细胞株，研究其在体内外对上皮性卵巢癌自噬、增殖、侵袭、铁死亡的影响及可能存在的分子机制，为上皮性卵巢癌的诊疗提供潜在的靶点。

Epithelial ovarian cancer(EOC) threatens women's health. Its etiology and pathogenesis are still unclear. Our previous research found that circRNA could affect EOC’s malignant progress by regulating celluar autophagy. In this study ,we used high-throughput sequencing technology and bioinformatics analysis to selected circ-RAB11FIP1 by activating autophagy in EOC.Further studies have confirmed that circ-RAB11FIP1 is highly expressed in epithelial ovarian cancer tissues and induce autophagy.It also interacts with miR-129, which may affect the expression of ATG7 and GPX4. Therefore, we hypothesis circ-RAB11FIP1 may promote autophagy in epithelial ovarian cancer by by sponging miR-129 to regulate the expression of ATG7. Meanwhile it could affect the expression of GPX4 and inhibits ferroptosis.We propose to construct silencing and over-expression cell lines of circ-RAB11FIP1, and find its’ effects on celluar autophagy, proliferation , invasion and ferroptosis of EOC in vivo and in vitro, meanwhile exploring the possible molecular mechanism. The study may provide a potential new target for the treatment of EOC.