EBNA1BP2 (EBP2) promotes the progression of hepatocellular carcinoma through upregulating the expression of MCM8 and HMGB1.

Primary liver cancer ranks among the most prevalent and refractory malignant tumors globally. This investigation delves into the role of Epstein-Barr virus nuclear antigen 2-binding protein (EBP2) in hepatocellular carcinoma (HCC). Significantly, EBP2 exhibits marked overexpression in HCC tissues, a finding that correlates with advanced tumor staging and unfavorable prognostic outcomes. In HCC cells, EBP2 silencing led to attenuated proliferation, enhanced apoptosis, and reduced migratory capacity, coupled with reversal of epithelial-mesenchymal transition (EMT). In vivo studies further demonstrated that EBP2 depletion potently suppressed tumor growth in xenograft models. Mechanistically, EBP2 interacts with CENPA to transcriptionally upregulate minichromosome maintenance protein family member 8 (MCM8), thereby stabilizing the MCM8/MCM9 complex and enhancing homologous recombination-mediated DNA repair. Functional rescue experiments revealed that MCM8 overexpression abrogated the suppressive effects of EBP2 knockdown on HCC cell proliferation and migration. In parallel, EBP2 regulates HMGB1 expression through the CENPA/YY1 transcriptional complex, thereby participating in the progression of HCC. Collectively, these findings highlight EBP2 as a crucial regulator of HCC progression via the dual axes-EBP2-CENPA-MCM8 and EBP2-CENPA/YY1-HMGB1, offering a promising therapeutic target for HCC intervention.