eIF4A3/circ102004轴调控前列腺癌细胞侵袭和转移的机制研究

环状RNA在癌症发展中发挥着关键作用。我们前期研究发现circ102004在前列腺癌组织中高表达，并证实其促进前列腺癌细胞增殖和转移，但机制不明。前期运用高通量测序发现circ102004使EphA2表达上调，并通过生物信息学预测出circ102004有6个位点可吸附miR-520家族，且EphA2是miR-520靶基因。另外，我们发现circ102004转录产物上游区域有eIF4A3的8个结合位点，由此我们推测eIF4A3引导并促进circ102004的形成，通过miR-520/EphA2促进前列腺癌进展。本课题拟进一步明确circ102004发挥功能的机制，同时通过干扰或过表达miR-520和EphA2，探讨其表达变化对癌细胞迁移、侵袭的影响；荧光素酶、pulldown等实验，阐明circ102004的来源是否依赖于eIF4A3的诱导，并探讨circ102004作为治疗靶点的可行性。

Circular RNA molecules (circRNA) play a key role in cancer development. In the early stage, we found that circ102004 was highly expressed in prostate cancer tissues by chip and qPCR, and it was confirmed by in vivo and in vitro experiments to promote prostate cancer cell proliferation, anti-apoptosis and metastasis. However, the mechanism of its function is not clear. We used high-throughput sequencing to find that circ102004 up-regulated EphA2 expression, and predicted by bioinformatics that there are 6 sites in circ102004 that can adsorb the miR-520 family, and EphA2 is miR-520. Target gene. In addition, we found that the upstream region of the circ102004 transcript has eight binding sites for eIF4A3, and we speculate that eIF4A3 leads and promotes the formation of circ102004, promoting prostate cancer progression through miR-520/EphA2. This study intends to further clarify the mechanism of function of circ102004, and at the same time, by interfering with or overexpressing miR-520 and EphA2, the effects of expression changes on cancer cell migration and invasion are discussed at the level of cell and animal model; luciferase and pulldown experiments confirm each other. Combine. At the same time, through RNAi technology, RIP, pulldown experiments, to clarify whether the source of circ102004 is dependent on the induction of eIF4A3, and to explore the feasibility of circ102004 as a therapeutic target.