肿瘤微环境是促进肿瘤生长与转移过程的关键调控因素，缺氧微环境是实体瘤常见现象。HIF1α是主要缺氧调节因子，通过增强相关基因转录，影响肿瘤代谢、存活、增殖、侵袭与转移，HIF1α功能受到蛋白稳定性、mRNA翻译、与转录水平调控。研究发现SVIL存在三个剪切异构体，SV1/SV4/SV5。缺氧上调SV4/SV5表达，与HIF1α呈相同趋势。我们最新结果显示SVIL是HIF1α上游调节因子，通过HIF1α促进上皮-间质细胞转换、新生血管生成等。但缺氧微环境引起SVIL促HIF1α转录、SVIL-HIF1α信号轴促肿瘤转移的作用机制仍不明了。我们拟采用分子、细胞与实验动物等手段，进一步解析缺氧诱导SVIL-HIF1α信号轴促肝癌转移的机制；揭示缺氧环境下SVIL相互作用网络、信号传导途径、表观修饰增强HIF1α转录方式；探索缺氧下SVIL表达异常的病理机制，为相关疾病干预与临床研究提供理论基础。

The tumor microenvironment is widely recognized as a key player in the promotion of tumor growth and malignant progression. Hypoxia is a major phenomenon in all solid tumour microenvironments. HIF1α (Hypoxia-inducible factor 1 alpha) is a primary regulator of the transcriptional response to hypoxia by regulating large numbers of genes involved in glycolysis, cell survival, proliferation, invasion and metastasis. The function of HIF1α was affected by protein stability, mRNA translation and gene transcription in hypoxia. We found three different splicing isoforms of SVIL (Supervillin), SV1/SV4/SV5, exist in tumour cells. Among of them, SV4 and SV5 protein levels linearly increase in accord with HIF1α to hypoxia. Our recently data shows SVIL is an upstream regulator of HIF1α through enhancing its transcription, thereby to regulate epithelia to mesenchymal transition (EMT) and angiogenesis in hypoxia. However, it is still very limited to the understanding of molecular mechanism of SVIL to regulate the transcription of HIF1α and enhance tumour metastasis by SVIL-HIF1α axis in hypoxia microenvironment. We propose to combine molecular biology, cell biology and experimental animal model to further dissect the properties of SVIL-HIF1α axis in regulation of HCC metastasis in hypoxia. Our aim is to identify SVIL interaction partners in hypoxia and reveal the regulatory effect by the interaction network, the signaling pathway and epigenetic modification in regulation of HIF1α transcription. Furthermore, we try to explore the pathological mechanism of the disease resulted from the abnormal expression of SVIL in hypoxia, which will provide theoretical basis for intervention of diseases and lay out a solid foundation for future clinical research.