State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing, 100005, China.
Department of Blood Transfusion, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
J Transl Med. 2024 Mar 8;22(1):254. doi: 10.1186/s12967-024-04976-4.
Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related hepatocarcinogenesis.
HBV-positive human liver cancer tissues were checked for PTEN expression. Transgenic HBV, Alb-Cre and Pten mice were inter-crossed to generate WT, HBV, Pten and HBV; Pten mice. Immunoblotting, histological analysis and qRT-PCR were used to study these livers. Gp73 mice were then mated with HBV; Pten mice to illustrate the role of hepatic tumor biomarker golgi membrane protein 73 (GP73)/ golgi membrane protein 1 (GOLM1) in hepatic oncogenesis.
Pten deletion and HBV transgene synergistically aggravated liver injury, inflammation, fibrosis and development of mixed hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). GP73 was augmented in HBV; Pten livers. Knockout of GP73 blunted the synergistic effect of deficient Pten and transgenic HBV on liver injury, inflammation, fibrosis and cancer development.
This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration.
虽然乙型肝炎病毒（HBV）感染是肝癌的主要危险因素，但大多数 HBV 携带者不会发展为这种致命疾病。因此，在肝肿瘤发生过程中涉及到其他分子改变。由于磷酸酶和张力蛋白同系物（PTEN）在大约一半的肝癌中减少，我们研究了 PTEN 缺陷在 HBV 相关肝癌发生中的意义。
检查 HBV 阳性肝癌组织中的 PTEN 表达。转染 HBV、Alb-Cre 和 Pten 小鼠进行杂交，生成 WT、HBV、Pten 和 HBV;Pten 小鼠。使用免疫印迹、组织学分析和 qRT-PCR 研究这些肝脏。然后将 gp73 小鼠与 HBV;Pten 小鼠交配，以说明肝肿瘤生物标志物高尔基膜蛋白 73（GP73）/高尔基膜蛋白 1（GOLM1）在肝肿瘤发生中的作用。
Pten 缺失和 HBV 转基因协同加重肝损伤、炎症、纤维化和混合肝细胞癌（HCC）和肝内胆管癌（ICC）的发展。HBV;Pten 肝脏中的 GP73 增加。GP73 的敲除削弱了 Pten 缺失和 HBV 转基因对肝损伤、炎症、纤维化和癌症发展的协同作用。
这种混合 HCC-ICC 小鼠模型模拟了携带 HBV 感染和 PTEN/AKT 信号通路改变的肝癌患者。针对 GP73 是治疗 HBV 感染和 PTEN 改变的癌症患者的一种有前途的治疗策略。
