Partial abrogation of FXR-KNG1 signaling by carboxyl-terminal truncated HBx-C30 in hepatitis B virus-associated hepatocellular carcinoma

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 as 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.

Automated summary

The study found that both full-length HBx and HBx C-terminal truncation coexist in HCC, and both can activate FXR signaling. Additionally, HBx-C30 has a weaker coactivating effect on FXR-KNG1 signaling compared to full-length HBx.