LncRNA-YAP、TEADs环路调控鼻咽癌上皮间质转化的机制研究

Nasopharyngeal carcinoma is one of the most common malignant tumor, which has a high transfer rate and attack rate. Despite some progress in treatment, the prognosis of the patients is still poor. The study of the molecular mechanism of tumor metastasis is still not fully clear currently, some studies show that the tumor metastasis is closely related to the transformation of epithelial mesenchymal. Hippo-YAP pathway is an important signaling pathways that was found in recent years, the pathways through regulating the activity of YAP control the cell proliferation and apoptosis, which plays an very important role in the occurrence of tumor. Our previous studies have found that YAP high expression intumor tissue and nasopharyngeal carcinoma (NPC) cells, promote the transfer of tumor proliferation, through the chip select relevant lncRNA YAP induced tumor proliferation and through preliminary experiments show that PVT1 can promote the proliferation of the tumor and EMT effect, and there may be a positive feedback loop between YAP and PVT1. On this basis, our study use some methods, such as hromatin immune coprecipitation, RNA coprecipitation, immune coprecipitation, luciferase report system, subcutaneous transplantation tumor experiment to elucidate the relationship between the YAP and PVT1, and the interaction mechanism. We can set a scientific foundation for further understanding the role of the YAP and PVT1, and their molecular mechanism in nasopharyngeal carcinoma.

鼻咽癌是具有高转移率和侵袭率的最常见恶性肿瘤之一,虽然治疗上取得进展，但晚期转移病人预后仍然极差，目前对其肿瘤转移的分子机制尚不完全清楚，研究显示与上皮间质转化密切相关。Hippo-YAP通路是近年来发现的重要信号通路，该通路通过调控YAP的活性控制细胞增生和凋亡，在肿瘤的发生中起到重要作用。我们前期研究发现YAP在鼻咽癌肿瘤组织及细胞中高表达，促进肿瘤增殖转移，通过芯片筛选出YAP诱导肿瘤增殖相关的lncRNA并通过预实验证明，PVT1能够起到促进肿瘤增殖及EMT作用，且与YAP之间可能存在正反馈环路。在此基础上，本课题将综合利用染色质免疫共沉淀、RNA免疫共沉淀、免疫共沉淀、荧光素酶报告系统、皮下移植瘤等实验阐明YAP与PVT1之间的相互作用机制，揭示其重要作用，为深入认识YAP及PVT1在鼻咽癌中的功能及分子机制奠定科学基础。

鼻咽癌是具有高转移率和侵袭率的最常见恶性肿瘤之一,虽然治疗上取得进展，但晚期转移病人预后仍然极差，目前对其肿瘤转移的分子机制尚不完全清楚，研究显示与上皮间质转化密切相关。Hippo-YAP通路是近年来发现的重要信号通路，该通路通过调控YAP的活性控制细胞增生和凋亡，在肿瘤的发生中起到重要作用。我们前期研究发现YAP在鼻咽癌肿瘤组织及细胞中高表达，促进肿瘤增殖转移，通过芯片筛选出YAP诱导肿瘤增殖相关的lncRNA并通过预实验证明，PVT1能够起到促进肿瘤增殖及EMT作用，且与YAP之间可能存在正反馈环路。依托该项目，我们明确了 PVT1 对鼻咽癌具有调控作用，能促进肿瘤增殖及EMT，证明其在肿瘤治疗中的潜在靶点价值。证明了YAP 和 PVT1 存在正反馈环路，为进一步开发新的靶向药物提供实验依据。明确了YAP 和 PVT1 在鼻咽癌肿瘤组织中的表达相关性及肿瘤预后的相关性，确定其能作为临床预后判断的新指标。