IncRNA TUG1通过EZH2介导DNA甲基化调控软骨肉瘤发生发展及机制研究

软骨肉瘤是常见的原发恶性骨肿瘤，治疗手段比较局限。调控肿瘤高表达基因日益引起关注，靶向治疗在软骨肉瘤中的作用也日益凸显。课题组前期发现软骨肉瘤中SFRP5启动子高度甲基化，组蛋白-赖氨酸N-甲基转移酶（EZH2）介导下游基因启动子甲基化，促进肿瘤增殖、侵袭和转移。文献表明lncRNA参与肿瘤甲基化调控而促进肿瘤的进展。IncRNA TUG1在多种肿瘤中高表达，可调控上皮-间质转化，促进肿瘤增殖转移，但作用机制尚未阐明。预实验表明IncRNA TUG1在软骨肉瘤中高表达，生信预测IncRNA TUG1能够募集EZH2。由此推测：IncRNA TUG1通过EZH2介导DNA甲基化调控软骨肉瘤发生发展。因此，本研究将通过临床检测和体内外实验验证上述假说，进一步阐明DNA甲基化与lncRNAs相互作用调控肿瘤相关基因表达及其机制，这将为软骨肉瘤的临床诊断和靶向治疗提供新的标志物和治疗靶点。

Chondrosarcoma is a common primary malignant bone tumor with limited treatment. The role of target therapy in chondrosarcoma is becoming more and more prominent. In the early stage, the research group found that the SFRP5 promoter was highly methylated in chondrosarcoma, and the real histone - lysine n-methyltransferase (EZH2) mediates the methylation of the downstream gene promoter, which promotes tumor proliferation, invasion and metastasis. Literature has shown that lncRNA is involved in tumor methylation regulation and promotes tumor progression. IncRNA TUG1 is highly expressed in a variety of tumors, which can regulate epithelial-mesenchymal transformation and promote tumor proliferation and metastasis. Preliminary experiments showed that IncRNA TUG1 was highly expressed in chondrosarcoma, and bioxin predicted that IncRNA TUG1 could recruit EZH2. This suggests that IncRNA TUG1 regulates the development of chondrosarcoma through EZH2-mediated DNA methylation. Therefore, this study will verify the above hypothesis through clinical detection and in vivo and in vitro, further elucidate the interaction between DNA methylation and lncRNAs to regulate tumor-related gene expression and its mechanism, which will provide new markers and therapeutic targets for clinical diagnosis and target therapy of chondrosarcoma.