circPUM1通过结合hnRNPH1蛋白促进脑胶质瘤恶性进展的分子机制研究

环状RNA(circRNA)作为结构特殊的RNA分子是该领域的研究热点。尽管circRNA在癌症中有诸多研究，但调控脑胶质瘤恶性进展机制不明。我们前期研究发现：circPUM1与脑胶质瘤恶性进展及预后相关；功能实验证实敲低circPUM1抑制脑胶质瘤增殖、迁移和成瘤能力；分子生物学实验揭示circPUM1与已知促癌剪切因子hnRNPH1存在互作；信息学分析显示circPUM1影响受hnRPNH1调控的可变剪切事件；提示circPUM1通过结合hnRNPH1调控可变剪切事件是脑胶质瘤恶性进展的潜在分子机制。本项目将研究：①circPUM1与hnRNPH1的互作位点；②circPUM1通过hnRNPH1调节可变剪切在脑胶质瘤恶性进展中作用；③在PDX模型中干预circPUM1对脑胶质瘤恶性进展的影响。旨从circRNA层面揭示脑胶质瘤恶性进展的分子机制，为改善脑胶质瘤诊疗提供理论依据和新思路。

Circular RNA (circRNA) as a class of RNA molecules with special structure is a research hotspot in this field. Although there are many studies on circRNA in cancer, the mechanism of regulating malignant progression of glioma is still unclear. Our previous research found that circPUM1 is associated with malignant progression and prognosis of gliomas; functional experiments confirmed that knocking down circPUM1 can inhibit the proliferation, migration and tumorigenic ability of gliomas; molecular biology experiments showed that circPUM1 interacts with the known cancer-promoting factor hnRNPH1; bioinformatics analysis suggested that circPUM1 is associated with alternative splice events regulated by hnRNPH1. The hypothesis was proposed that circPUM1 combined with hnRNPH1 to regulate alternative splice events is a potential molecular mechanism of malignant progression of glioma. This project will study: ① the interaction site of circPUM1 and hnRNPH1; ② the role of circPUM1 in regulating malignant progression of glioma by binding hnRNPH1 protein; ③ the effect of circPUM1 intervention on the malignant progression of glioma in PDX model. The purpose is to reveal the molecular mechanism of glioma malignant phenotype from the circRNA level, and provide theoretical basis and new ideas for improving the clinical diagnosis and treatment of glioma.