Background
Hepatitis B virus (HBV) infection can exacerbate liver disease progression through multiple mechanisms, eventually leading to hepatocellular carcinoma (HCC). HBV-encoded oncogene X protein (HBx), a key regulatory protein of HBV infection, serves as a positive regulator of hepatocarcinogenesis. The indispensability of the M2 subunit of ribonucleotide-diphosphate reductase (RRM2) lies in its role in facilitating DNA replication and repair processes. In our previous investigation, it was postulated that the gene RRM2 exhibits elevated expression levels in several categories of malignant tumors, particularly in HBV-related HCC. Additionally, it was observed that RRM2 is present within protein complexes that are centered on HBx. In the present investigation, the
Conclusions
Therefore, we hypothesised that RRM2 is a potential downstream target of HBx-induced hepatocarcinogenesis, and mining the oncogenic mechanism of RRM2 is significant in exploring the preventive treatment of HBV-related HCC.
Results
This work initially investigated the impact of suppressing cellular autophagy on the malignant biological behaviors of HBx-promoted cells using an in vitro cellular model. The findings revealed that the suppression of cellular autophagy partially disrupted the oncogenic effects of HBx. In light of this, we proceeded to conduct more investigations into the regulatory association between RRM2 and HBx-induced autophagy in the upstream-downstream context. Our data indicate that HBx proteins increase the expression of RRM2. Suppression of RRM2 expression not only hinders HBx-induced autophagy, but also worsens the cellular G1/S blockage and reduces the HBx-induced malignant growth of hepatocellular carcinoma tumors, while stimulating apoptosis. Conclusions: Therefore, we hypothesised that RRM2 is a potential downstream target of HBx-induced hepatocarcinogenesis, and mining the oncogenic mechanism of RRM2 is significant in exploring the preventive treatment of HBV-related HCC.