ASF1B Serves as a Potential Therapeutic Target by Influencing Cell Cycle and Proliferation in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high morbidity and mortality. Therefore, it is very important to find potential biomarkers that can effectively predict the prognosis and progression of HCC. Recent studies have shown that anti-silencing function 1B (ASF1B) may be a new proliferative marker for tumor diagnosis and prognosis. However, the expression and function of ASF1B in hepatocellular carcinoma remain to be determined. In this study, integrated analysis of the Cancer Genome Atlas (TCGA), genotypic tissue expression (GTEx), and Gene Expression Omnibus (GEO) databases revealed that ASF1B was highly expressed in HCC. Kaplan-Meier survival curve showed that elevated ASF1B expression was associated with poor survival in patients with liver cancer. Correlation analysis of immune infiltration suggested that ASF1B expression was significantly correlated with immune cell infiltration in HCC patients. Gene set enrichment analysis (GSEA) indicated that ASF1B regulated the cell cycle, DNA Replication and oocyte meiosis signaling. Our experiments confirmed that ASF1B was highly expressed in HCC tissues and HCC cell lines. Silence of ASF1B inhibited hepatocellular carcinoma cell growth in vitro. Furthermore, ASF1B deficiency induced apoptosis and cell cycle arrest. Mechanistically, ASF1B knockdown reduced the expression of proliferating cell nuclear antigen (PCNA), cyclinB1, cyclinE2 and CDK9.Moreover, ASF1B interacted with CDK9 in HCC cells. Taken together, these results suggest that the oncogenic gene ASF1B could be a target for inhibiting hepatocellular carcinoma cell growth.