近年的研究表明，lncRNA在肿瘤的发生发展、转移、复发和耐药等过程中有着重要的调控作用。我们鉴定了一个新的lncRNA,即TCL6, 在耐药性肿瘤组织中低表达。上调lncRNA TCL6的表达可恢复耐药性肾癌细胞对sunitinib的敏感性，以及可抑制细胞的增殖。我们发现lncRNA TCL6在肾癌中表达降低并且与肾癌进展及患者预后密切相关。此外，我们还证实lncRNA TCL6能够与β-catenin和PML相互作用。因此，我们提出假说在肾癌发展过程中，lncRNA TCL6可能通过调节β-catenin和PML的功能，从而调节肾细胞癌的发生发展和sunitinib耐药。在此基础上，本课题拟通过一系列体内和体外实验研究lncRNA TCL6在肾癌发生发展、肿瘤干细胞以及耐药中的作用机制，为肾癌的lncRNA研究提供新的线索，并为肾癌的诊断和治疗提供新的理论依据和药物靶点。

Recent studies suggested that lncRNA is involved in cancer initiation, progression, metastasis, recurrence and drug resistance. Here we identified an lncRNA, TCL6, which low-expressed in sunitinib-resistant tumors. We found that up-regulation of lncRNA TCL6 in resistant cells resulted in a notably repressed growth upon sunitinib treatment. We found that lncRNA TCL6 was significantly associated with tumor progression and prognosis. Furthermore, we demonstrated that lncRNA TCL6 interact with β-catenin and PML. We therefore propose a hypothesis that lncRNA TCL6 may act as a key regulator of sunitinib-resistance and tumorigenesis of renal cancer by regulating β-catenin and PML. In this project, we plan to systematically study the function and the molecular mechanism of lncRNA TCL6 in renal cancer development, progression, stem cell function and sunitinib-resistance by a variety of in vitro and in vivo assays, which will uncover the mechanism of lncRNA TCL6 in ccRCC and propose a new sight to the lncRNA research in ccRCC, and which will benefit the diagnosis and treatment of ccRCC.