m6A修饰介导的lncRNA WEE2-AS1转录后novel-pri-miRNA剪切机制在胶质瘤恶性进展中的作用研究

胶质瘤是中枢神经系统最常见的恶性肿瘤，研究表明lncRNA在其恶性进展中起关键作用，并受到m6A修饰的调控。我们前期研究发现，胶质瘤中显著上调的lncRNA中，WEE2-AS1存在最高水平的m6A修饰，且与肿瘤细胞增殖和患者的不良预后密切相关。预实验提示该m6A修饰位点与WEE2-AS1转录后可变剪接及pri-miRNA成熟加工过程密切相关。据此我们提出了lncRNA WEE2-AS1转录后可变剪切形成的novel_LNC_007894作为潜在的pri-miRNA，在m6A修饰的介导下剪切为novel-miR-815，进而通过靶向MYT1L等抑癌基因通路促进胶质瘤恶性进展的新假说。本课题拟采用RNA可变剪切和m6A修饰研究策略，在体内外深度解析WEE2-AS1在胶质瘤恶性进展中的作用机制，并针对该关键lncRNA及其相关m6A调控分子设计干预方案，将为胶质瘤靶向治疗策略的研发提供重要参考。

Glioma is the most common malignant tumor, while recent researches demonstrate that lncRNA plays a vital role in glioma progression under the regulation m6A modification. Our previous research showed that WEE2-AS1 was the only with high m6A modification among those lncRNAs upregulated in glioma and that WEE2-AS1 was associated with glioma cell proliferation and poor prognosis in glioma patients. In preliminary study, we found that m6A modification is closely related to post-transcriptional splicing of WEE2-AS1 and pri-miRNA maturation。Therefore, we proposed that WEE2-AS1 could be spliced into novel_LNC_007894, becoming a potential pri-miRNA, and further processed into novel-miR-815, to target several tumor suppressor pathways including MYT1L and promote glioma progression. In this research, we planned to employ RNA splicing and m6A modification strategies to deeply explore the role of WEE2-AS1 in glioma progression both in vivo and vitro and design corresponding interventions, providing significant reference to novel glioma targeted therapy.