现有研究证据表明人SAMD9/SAMD9L基因在宿主细胞防御病毒感染以及调控炎症反应中发挥重要作用。我们前期研究结果表明，SAMD9L基因在乙肝病毒相关性肝癌病人中频繁发生遗传学突变、表达失调下降而失活，进一步干扰SAMD9L基因在肝癌细胞中的表达能够加快细胞周期S期进入从而促进细胞体外生长、克隆形成以及裸鼠成瘤性，提示SAMD9L基因在HBV相关性肝癌发生发展中发挥重要的抑癌作用。本项目提出SAMD9/SAMD9L基因失活引起肝细胞对HBV病毒感染的防御能力减弱、炎症反应增强，最终导致了HBV相关性肝癌的发生、发展。因此，本项目拟研究SAMD9/SAMD9L基因在肝细胞防御HBV病毒感染中的作用以及SAMD9/SAMD9L基因在肝细胞防御HBV感染以及调节炎症反应中的作用及相关分子机制，为抗HBV感染治疗、预防肝炎以及肝癌建立理论基础。

Present available research evidences suggest that human SAMD9/SAMD9L gene play an important role in host defense against viral pathogens and modulating inflammatory responses. Our previous research showed that SAMD9L was frequently inactivated by somatic mutations and deregulated expression in hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV), and then RNA interference against SAMD9L promoted cell proliferation, colony formation and tumorigenicity in vivo via facilitating G1-S transition of cell cycle progression. These findings suggest that SAMD9L has an important suppressive role in HBV-related HCC. This research project proposes that SAMD9/SAMD9L inactivation caused by genetic lesions and deregulated expression led to imperfect defense against HBV infection and enhanced inflammation, ultimately the initiation and development of HBV-related HCC. Hence, this study plans to investigate the roles and molecular mechanisms of SAMD9/SAMD9L genes in the defense against HBV and mediating inflammatory responses, and establish a theoretical basis for the therapy of anti-HBV infection as well as prevention of hepatitis, hepatocellular carcinoma.