ENO1 interacts with PKM to promote HBV-related hepatocellular carcinoma progression and HBV replication.

The progression of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) is driven by complex interactions between metabolic reprogramming and viral replication. Glycolytic enzymes, including α-enolase (ENO1) and pyruvate kinase M (PKM), play key roles in tumor progression, but their specific contribution to HBV-associated HCC remains inadequately defined. This study investigates the molecular mechanisms by which ENO1 and PKM promote HCC progression and HBV replication. The expression levels of ENO1 and PKM in HBV-infected HCC cells were evaluated, and their interaction was explored using co-immunoprecipitation (Co-IP), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot analysis. Additionally, an HCC mouse model was employed to assess the impact of this interaction on HCC progression and HBV replication. Both ENO1 and PKM were significantly upregulated in HBV-associated HCC cells and mouse models. Co-IP assays revealed a direct interaction between ENO1 and PKM. Functionally, ENO1 enhanced HCC cell proliferation, migration, invasion and in vivo tumor growth. Furthermore, elevated levels of ENO1 and PKM significantly increased HBV replication, thus exacerbating HCC progression. This study indicated a novel mechanism in which ENO1 interacts with PKM to accelerate both HBV-related HCC progression and viral replication. These findings suggest that targeting the ENO1-PKM axis may provide a promising metabolic therapeutic approach for HBV-associated HCC.