TRAF7相关的炎症信号通路在肝癌发生发展的肿瘤微环境中的作用和机制研究

目前我国肝癌死亡率高居恶性肿瘤第二位，但由于缺乏有效的治疗靶点，肝部分切除术后的高复发率仍是肝癌治疗所面临的巨大挑战。研究表明肝癌及其间质中参与免疫和炎症反应调节的基因谱系变化同样能够反映HCC的进展。我们的前期工作发现肿瘤坏死因子受体相关蛋白家族（TRAF）成员之一的TRAF7在肝癌组织中表达上调，并且通过其E3泛素连接酶活性介导了转录因子KLF4和NF-kB等的蛋白稳定性，从而影响了二者的转录活性，进而参与了对肝癌细胞增殖、迁移以及炎症信号通路传导的调控。本研究旨在前期工作的基础上进一步探讨TRAF7及其所介导的炎症信号通路在肝癌的发生进展以及肿瘤微环境中的功能和分子机制，以期能够为肝癌的预后评估提供高灵敏度和高特异性的分子标志物谱，并为肝癌的个体化治疗提供新的靶点。

The mortality rate of liver cancer is second in malignant tumor in China since lack of effectively early diagnosis method and high rate of relapse and metastasis. It have reported that the molecules involved in inflammatory and immunologic responses in liver cancer and its mesenchyme also indicate the tumor progression. Our previous works have demonstrated TNF receptor associated protein family (TRAF)7 was up-regulated in liver cancer. It regulates the protein stability of transcriptional factors including KLF4 and NF-kB through the activity of E3 ubiquitin ligase, which influenced the proliferation and migration of liver cancer cells and the transduction of inflammatory signaling pathway. In this research, we expect to further elucidate the function and mechanism of TRAF7 and its associated inflammatory signaling pathway in liver cancer, in order to provide the new molecular markers of prognosis evaluation and potential targets of individual therapy for liver cancer.