Department of Pharmacology, Shantou University Medical College, Guangdong, China.
Department of Oncology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Virus Res. 2021 Feb;293:198264. doi: 10.1016/j.virusres.2020.198264. Epub 2021 Jan 2.
Hepatitis B virus (HBV) X protein (HBx) is a key regulator of HBV-associated hepatocarcinogenesis. C-terminal-truncated HBx is frequently detected in hepatocellular carcinoma (HCC). The role of HBx, especially C-terminal-truncated HBx, in HCC pathogenesis has been controversial. To elucidate the biological role of C-terminal-truncated HBx underlying HBV-associated hepato-oncogenesis, we constructed a vector expressing HBx-C30 (deletion of 30 aa from the C terminus of HBx) and functionally analyzed its regulation on farnesoid X receptor (FXR) signaling, which is known to inhibit hepatocarcinogenesis. In the present study, we found full-length HBx and HBx C-terminal truncation coexist in HCC, and both full length HBx and HBx-C30 can activate FXR signaling. Moreover, HBx-C30 weakly coactivates FXR-KNG1 signaling compared to full-length HBx.
乙型肝炎病毒（HBV）X 蛋白（HBx）是 HBV 相关肝癌发生的关键调节因子。在肝细胞癌（HCC）中经常检测到 C 末端截断的 HBx。HBx，特别是 C 末端截断的 HBx，在 HCC 发病机制中的作用一直存在争议。为了阐明 C 末端截断的 HBx 在 HBV 相关肝肿瘤发生中的生物学作用，我们构建了表达 HBx-C30（HBx C 末端缺失 30 个氨基酸）的载体，并对其调节法尼醇 X 受体（FXR）信号的功能进行了分析，已知 FXR 信号可抑制肝癌的发生。在本研究中，我们发现全长 HBx 和 HBx C 末端截断同时存在于 HCC 中，全长 HBx 和 HBx-C30 均可激活 FXR 信号。此外，HBx-C30 与全长 HBx 相比，对 FXR-KNG1 信号的弱共激活作用。
