缺氧是促进肝细胞癌（HCC）侵袭转移的关键因素，但具体机制仍很不清楚。课题组发表成果证实缺氧通过调控基因和miRNAs发挥促HCC功能。我们前期发现①缺氧诱导HCC细胞高表达lncRNA RUNX1-IT1；②HCC组织中RUNX1-IT1高表达提示患者预后不良；③RUNX1-IT1促进HCC侵袭和迁移，miR-875-5p、EIF3A及TGF-β1/SMAD通路在此过程中可能发挥调控作用。因此，我们拟通过临床和功能学实验证实如下科学假说：缺氧肿瘤微环境中HIF-1α直接激活RUNX1-IT1转录，RUNX1-IT1通过竞争性结合miR-875-5p解除EIF3A的表达抑制，EIF3A通过TGF-β1/SMAD通路促进HCC侵袭转移。本项目将揭示RUNX1-IT1在HCC侵袭转移中的功能和调控机制，探索靶向干扰RUNX1-IT1的抗HCC作用，从而为临床上开发新HCC靶向治疗策略提供依据。

Hypoxia is the critical reason for promoting the invasion and metastasis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains poorly known. Our published data verify that hypoxia promotes HCC progression via regulating genes and miRNAs expression. Our pre-experiments found that hypoxia induced upregulation of lncRNA RUNX1-IT1 in HCC cells. High RUNX1-IT1 expression indicated poor prognosis of HCC patients. RUNX1-IT1 promoted invasion and migration of HCC cells, miR-875-5p, EIF3A and TGF-β1/SMAD pathway possibly exerted an critical regulatory role in this process. Thus, clinical and biological experiments will be carried out to verify the following scientific hypothesis that HIF-1α directly activates RUNX1-IT1 transcription in hypoxia-related tumor microenvironment. Subsequently, RUNX1-IT1 relieves EIF3A expression inhibition by competitively binding to miR-875-5p. EIF3A restoration promotes invasion and metastasis of HCC cells via TGF-β1/SMAD signaling pathway. Thus, this project will reveal the function and regulatory mechanism of RUNX1-IT1 in the invasion and metastasis of HCC, and explore the anti-HCC effect by targeting RUNX1-IT1, providing a basis for the clinical development of new HCC targeted therapies.