浸润型肺腺癌患者由于肿瘤的转移，其生存率明显低于原位型和微小浸润型肺腺癌。前期研究表明HOTAIR表达增高与肺腺癌患者预后差及淋巴结转移呈正相关，HOTAIR增强肺腺癌转移与侵袭能力。同时检测到14-3-3σ在肺腺癌中表达与HOTAIR呈正相关，而靶向14-3-3σ的miR-638与HOTAIR表达负相关。14-3-3σ通过调控细胞骨架动力学促进肿瘤转移。由此，我们提出科学假设：HOTAIR负性调控miR-638/14-3-3σ轴促进肺腺癌的转移。本项目首先在细胞和动物模型中探讨HOTAIR/14-3-3σ在肺腺癌转移中的功能及对细胞骨架的调控；其次验证HOTAIR通过沉默miR-638上调14-3-3σ的分子机制；最后，从大样本回顾性分析中总结HOTAIR/miR-638/14-3-3σ对于肺腺癌及转移的临床相关性和预后判断价值。

The survival rate of patients with invasive pulmonary adenocarcinoma is significantly lower than in in-situ and minimally invasive lung adenocarcinoma due to tumor metastasis. Our previous work showed that HOTAIR higher expression in patients with lung adenocarcinoma was positive correlation with poor prognosis and lymph node metastasis. HOTAIR could enhance the metastasis and invasion ability of lung adenocarcinoma cells. 14-3-3σ was also higher in lung adenocarcinoma with positive correlated with HOTAIR expression, and miR-638 targeted 14-3-3σ was negatively correlated with HOTAIR expression in lung adenocarcinoma. Previous reports have shown that 14-3-3σ directed cell migration and tumor invasion through regulating cytoskeletal dynamics. Based on these results, we propose that HOTAIR negatively regulates miR-638/14-3-3σ axis promoting the metastasis of lung adenocarcinoma. In this project, firstly, we should verify the roles of HOTAIR and 14-3-3σ in the metastasis of lung adenocarcinoma and mechanisms of regulation the cytoskeleton dynamics in cell and animal models. Secondly, it is studied that the molecular mechanism of HOTAIR raises the 14-3-3σ expression through silence the miR-638 in lung adenocarcinoma. Finally, HOTAIR/miR-638/14-3-3σ relations with the metastasis and prognosis of patients with lung adenocarcinoma were observed via retrospective analyses in large clinical samples.