我们的前期研究发现，肝癌细胞缺氧条件下发生上皮细胞间质化，且侵袭转移能力增强、导致索拉菲尼耐药。本研究将应用LncRNA芯片等技术获得肝癌细胞缺氧诱导后差异表达的长链非编码RNA（lncRNAs），并进一步利用qRT-PCR方法检测并验证lncRNAs在肝癌细胞系和组织中的表达，明确其与缺氧诱导因子HIF1ɑ表达的相关性；通过临床病例资料分析明确lncRNA与患者分期、分化、淋巴结转移、化疗敏感性、预后等的相关性。克隆、鉴定lncRNA全长并构建稳定表达的肝癌细胞系，通过克隆形成、增殖实验、凋亡、细胞周期检测、裸鼠成瘤等实验探索lncRNA在肝癌中的功能。利用CHIRP结合质谱分析和测序分析等技术明确与lncRNA相互作用的蛋白和DNA，探讨其所涉及的重要信号通路和作用机制。通过MTT实验探讨lncRNA表达缺失和稳定表达的肝癌细胞对索拉菲尼的敏感性，明确lncRNA是否参与索拉菲尼耐药机

Even through improved interventional and surgical treatment, the 5-year survival rate of Hepatocellular carcinoma (HCC) is less than 15%. The major reason is cancer recurrence and metastasis. Hypoxia is a common phenomenon in many solid tumors，promoting the proliferation, migration and invasion of tumor cells. Our previous studies have found that Hypoxia promoted Epithelial-mesenchymal transition (EMT) , invasion and metastasis of hepatic cancer cells by increasing the expression of HIF1ɑ. In addition, hypoxia induced drug resistance of cancer cells to sorafenib. In this study, human LncRNA microarray is used to detect and identify lncRNAs that are increased or reduced significantly by hypoxia in HCC cells. qRT-PCR is then used to verify the expression of these lncRNAs in HCC cell lines and tissues. SPSS 15.0 software was employed to analyze the correlation of lncRNAs expression and clinical factors of HCC patients. 5’RACE and 3’RACE was employed to gain the full-length sequence of lncRNA that will be cloned into expression vector to establish lncRNA stably expressed cell lines. Cell proliferation assay, flow cytometry analysis, colony formation and xenograft mice model will be applied to analyze the effect of lncRNA on HCC tumor growth. CHIRP combined with Mass Spectrometry and Sequencing are used to identify the proteins and DNAs that binds to lncRNA. Furthermore, MTT is used to detect the sensitivity of lncRNA unexpressed and stably expressed HCC cells to sorafenib.