CircPTK2通过结合endophilin A2促进膀胱癌侵袭转移的机制研究

易侵袭转移是膀胱癌重要的生物学特点，也是影响其治疗和预后的关键因素，但分子机制尚未阐明。已有研究表明环状RNA（circRNA）在膀胱癌组织中异常表达，并参与调控膀胱癌发生发展。我们前期研究发现circPTK2在膀胱癌细胞和组织中高表达，可促进膀胱癌侵袭转移。RNA pull down及质谱分析表明circPTK2可与endophilin A2结合，且沉默endophilin A2能明显削弱膀胱癌细胞迁移侵袭能力。由此我们提出circPTK2可能通过结合endophilin A2调控下游靶基因的表达，进而促进膀胱癌侵袭转移。本研究拟进一步应用体内、体外实验、高通量测序等技术，鉴定出circPTK2-endophilin A2轴调控的下游转移相关基因，获得circPTK2促进膀胱癌侵袭转移的可靠证据，并明确其临床意义，为其作为新的膀胱癌治疗靶点和预后标志物提供科学依据。

Susceptibility to invasion and metastasis is the important biological characteristic of bladder cancer, and it’s the critical factor affecting treatment and prognosis of bladder cancer. However, the molecular mechanisms remain to be further elucidated. Accumulating studies have implied that circRNAs are aberrantly expressed in bladder cancer, and they have been considered to mediate occurrence and development of bladder cancer. Our previous study found that circPTK2 was up-regulated in bladder cancer cell lines and tissues, and it could significantly promote invasion and metastasis of bladder cancer. Moreover, we identified that circPTK2 could bind to endophilin A2 by RNA pull down and mass spectrometry. Knockdown endophilin A2 attenuated the invasion and metastasis abilities of bladder cancer cells. Therefore, we propose a possible mechanism that circPTK2 binds to endophilin A2 to regulate the downstream target genes, and then facilitates invasion and metastasis of bladder cancer. To acquire reliable evidence of circPTK2 stimulating bladder cancer invasion and metastasis, we intend to apply in vivo and in vitro functional experiments, and high-throughput sequencing analysis to identify the related downstream genes regulated by circPTK2/endophilin A2 axis. Furthermore, we will elucidate the clinical significance of circPTK2, and provide a scientific basis that it can be used as a new therapeutic target and prognostic marker for bladder cancer