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.

The m6A/m5C/m1A Regulated Gene Signature Predicts the Prognosis and Correlates With the Immune Status of Hepatocellular Carcinoma

“…Preliminary evidence suggests that m6A/m1A/m5C regulated genes play important biological roles in the progression of HCC, which can be used to determine the prognosis and survival of HCC patients. The signaling pathways, including the cell cycle, DNA replication, and WNT are closely associated with cancer progression (28)(29)(30)(31)(32)(33)(34). Previous studies have found that ASF1B is highly expressed in HCC, and elevated ASF1B expression level is associated with poor prognosis in HCC patients.…”

“…The signaling pathways, including the cell cycle, DNA replication, and WNT are closely associated with cancer progression ( 28 – 34 ). Previous studies have found that ASF1B is highly expressed in HCC, and elevated ASF1B expression level is associated with poor prognosis in HCC patients.…”

“…GSEA revealed that ASF1B may regulate the cell cycle, DNA replication, and oocyte meiotic signaling pathway. ASF1B silencing inhibits the growth and cell cycle arrest, induces apoptosis, and reduces the expression levels of PCNA, cyclinB1, cyclinE2, and CDK9 in HCC cells ( 28 ). The level of TCF3 expression is significantly increased in HCC tissues.…”

Increased ASF1B Expression Correlates With Poor Prognosis in Patients With Gliomas

“…ASF1B has also been shown to play a role in the formation of lung adenocarcinoma tumors, and it was discovered that ASF1B may promote tumor growth by regulating the intermediate protein BCAR1 ( 35 ). Additionally, another study pointed out that the oncogene ASF1B may be the target of inhibiting the growth of hepatocellular carcinoma cells ( 36 ). Thus, ASF1B may participate in glioma tumorigenesis by regulating cell proliferation.…”

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“…ASF1B has been shown to play a role in the formation of lung adenocarcinoma tumors, and it was discovered that ASF1B may promote tumor growth by regulating the intermediate protein BCAR1 (35). Additionally, another study pointed out that the oncogene ASF1B may be the target of inhibiting the growth of hepatocellular carcinoma cells (36). Thus, ASF1B may participate in glioma tumorigenesis by regulating cell proliferation.…”