剪接因子LUC7L通过调节可变剪接事件促进肾透明细胞癌发展进程的机制研究

肾透明细胞癌（ccRcc）是泌尿系统主要恶性肿瘤之一，寻找有效的预后指标和治疗靶点对其治疗具有重要意义。可变剪接是调控基因表达的重要机制，异常的RNA剪接与肿瘤的发生发展密切相关。我们前期研究发现，剪接因子LUC7L在ccRcc组织中过表达，与患者较差的预后相关，并且参与调控了ccRcc中一系列核心剪接事件。但LUC7L在ccRcc发展中的作用及调控可变剪接的分子机制，尚不清楚。本项目将明确LUC7L在ccRcc中的功能，并在基因组范围探索LUC7L的靶基因，揭示LUC7L介导的剪接事件在ccRcc中的作用途径，鉴定LUC7L在pre-mRNA中的结合基序，绘制LUC7L调控可变剪接的RNA图谱，寻找与LUC7L协同发挥作用的剪接因子并确定它们之间相互作用的结合区域，从而阐明LUC7L调控可变剪接影响ccRcc发展的机制，为ccRcc的诊断和治疗提供新的靶点。

Clear cell renal cell carcinoma (ccRcc) is one of the main malignant tumors of urinary system. It is of great significance to search for effective prognostic indicators and therapeutic targets for ccRcc. Alternative splicing is an important mechanism to regulate gene expression and increase proteome diversity. Aberrant alternative splicing events are closely related to the occurrence and development of tumors. Our previous study found that splicing factor LUC7L was overexpressed in ccRcc tissue and was associated with poor prognosis of patients. Further analysis shows that some core splicing events in ccRcc may be regulated by LUC7L. However, the role of LUC7L in the development of ccRcc and the molecular mechanism underlying alternative splicing regulation are still unclear. This project will clarify the function of LUC7L in ccRcc, search for the target genes of LUC7L in the genome scope, reveal the pathways of LUC7L-mediated aberrant splicing in ccRcc, identify the binding site of LUC7L in pre-mRNA, draw the RNA map of LUC7L regulated alternative splicing, and identify the splicing factors that work together with LUC7L. The aim of this study is to elucidate the mechanism by which LUC7L regulate alternative splicing facilitating the development of ccRcc, and to provide new targets for the diagnosis and treatment of ccRcc.