circPTPRA结合IGF2BP1调控RNA甲基化识别在膀胱癌中的作用与机制研究

胰岛素样生长因子-2 mRNA结合蛋白1（IGF2BP1）是近来发现的促肿瘤发生发展关键因子，能够识别一系列N6-甲基腺嘌呤（m6A）修饰的mRNA并调控其稳定性。本研究前期对IGF2BP1进行了RNA免疫共沉淀结合高通量测序分析，通过与我们已报道的膀胱癌差异表达环状RNA数据库交叉比对，筛选出了具有潜在IGF2BP1蛋白结合能力的膀胱癌相关环状RNA（circPTPRA）。进一步研究显示：过表达circPTPRA能够减少IGF2BP1与靶基因mRNA的结合，并有效逆转IGF2BP1对膀胱癌细胞增殖侵袭能力的促进作用。本研究拟在此基础上，进一步解析circPTPRA在膀胱癌细胞浆中结合并阻断IGF2BP1蛋白对m6A修饰mRNA的识别、进而降低下游靶基因mRNA稳定性的作用及机制。本项目的成功实施，将丰富环状RNA的作用模式，并阐明RNA甲基化识别的内在调控方式，为膀胱癌治疗提供新依据。

Insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) is a key RNA-binding protein that plays important role in promoting tumorigenesis and development. IGF2BP1 can recognize a series of N6-methyladenine (m6A) modified mRNA and regulate their stability. In our previous study, IGF2BP1 was analyzed by RNA immunoprecipitation combined with high throughput sequencing. By cross-comparing with the differentially expressed circRNA database of bladder cancer reported by our recent work, circPTPRA was screened out. Further studies show that overexpression of circPTPRA can reduce the binding of IGF2BP1 to target mRNA, and effectively reverse the promotion of proliferation and invasion of bladder cancer cells by IGF2BP1. In this study, we intend to further elucidate the role and mechanism of binding between circPTPRA and IGF2BP1 in regulating RNA N6-methyladenosine recognition and reduction of the stability of downstream targeted mRNA. This work will enrich the mode of action of circRNA and elucidate the intrinsic regulation mode of RNA methylation recognition, as well as provide a novel basis for the treatment of bladder cancer.