肝癌发生与肝细胞感染乙型肝炎病毒（HBV）密切相关，近期我们研究发现HBV-x蛋白（HBx）优先驱动肝细胞表达甲胎蛋白（AFP）。病原微生物能诱导宿主细胞自然重编程，而细胞自然重编程是细胞恶性转化的细胞基础。PI3K/AKT信号在细胞重编程过程中发挥重要的作用，我们研究已证明AFP能激活肝细胞内的PI3K/AKT信号途径，而且发现PI3K/AKT信号激活能诱导白细胞介素-6（IL-6）及其受体表达，IL-6是诱导肝细胞恶性转化的重要分子，所以，我们推测AFP具有诱导肝细胞恶性转化的生物学功能。本项目将在体内和体外开展HBx对AFP基因表达的优先选择性，以及AFP表达后对IL-6及其受体的表达调控作用，探索AFP表达对驱动肝细胞自然重编程和恶性转化的影响及其作用机制。本项目研究将证明AFP是驱动肝癌发生的关键因子，对利用AFP表达预警肝癌发生和治疗肝癌的新靶点具有重要的科学意义和应用价值。

Develoment of hepatocellular carcinoma(HCC) was closely correlated with infection of hepatitis B virus(HBV). Recenetly, We have found that HBV x(HBx) protein priored to drive expression of alpha fetoprotein(AFP) during HBx induced hepatocarcinogenesis. Cells occured natural reprogram while infected with pathogenic microbiology, and natural reprogram of host cells were foundation for malignant transformation of cells. We have proved that AFP been able to activate phosphoinositide -3 kinase(PI3K)/protein kinase B(AKT), PI3K/AKT signal pathway played pivotal role on cells natural reprogram. Documents indicated that expression of interleukin-6(IL-6) and IL-6 receptor were regulated by PI3K/AKT signal, due to IL-6 was a critical molecules for inducing malignant transformation of the cells, we speculated that AFP harbors a function to stimulate malignant transformation of liver cells. In the project, we investigated how HBx induces the expression of AFP in vivo and in vitro, explore the effect and mechanism of AFP in driving malignant transformation of liver cells. This project will discover AFP is a pivotal factor for promoting development of HCC, AFP is applied as a early warning marker and therapeutic target of HCC patients.