肾癌术后复发转移是导致患者死亡的主要原因，但确切的分子机制尚未完全阐明。申请人及所在课题组长期聚焦肾癌的基础与临床相结合的工作，在非编码RNA与肾癌侵袭转移方面已取得一定的研究经验。我们通过芯片筛选发现，长链非编码RNA LBX2-AS1在肾癌组织中表达显著增高，且与患者的无疾病进展期呈负相关。此外，改变LBX2-AS1表达，其染色体临近区域的PCGF1表达和肾癌细胞EMT过程也出现相应改变，EMT则被认为介导肿瘤的侵袭和迁移过程。因此，我们推测LBX2-AS1通过调控PCGF1基因的表达，促进EMT过程，进而增强肾癌的侵袭和转移能力。本研究拟基于肾癌巢式队列患者临床样本及随访研究、PDX小鼠模型及相应的细胞模型，系统探索LBX2-AS1通过调控PCGF1介导肾癌侵袭转移的分子机制。本项研究将为今后遏制肾癌转移提供新的方法和研究思路。

Recurrence and metastasis are main causes of death in renal cell carcinoma (RCC) patients. However, exact mechanism has not been fully elucidated. The applicant and the research team have long focused on the work of basic and clinical studies in renal cell carcinoma, and have gained some experience in non-coding RNA and invasion and metastasis of RCC. Our microarray analyses showed that lncRNA LBX2-AS1 was significantly up-regulated in RCC. High LBX2-AS1 expression was correlated with decreased disease-free survival. While down-regulating LBX2-AS1 in RCC cells, the expression of PCGF1 and epithelial-mesenchymal transition (EMT) process was inhibited. EMT was thought to be participated in cancer invasion and metastasis. So we hypothesize that lncRNA LBX2-AS1 may targeted regulate PCGF1 expression and promote EMT process, thus increasing the ability of invasion and metastasis in RCC. This study is based on the clinical samples, follow-up study of RCC nested cohort, PDX mouse model and cell model, and hopes to systematically explore the molecular mechanism of LBX2-AS1 regulating invasion and metastasis of renal cell carcinoma via PCGF1.