promotes the oncogenicity of hepatocellular carcinoma via regulation of .

OBJECTIVE

Apurinic/apyrimidinic endonuclease 1 (APEX1), a key enzyme responsible for DNA base excision repair, has been linked to development and progression of cancers. In this work, we aimed to explore the role of APEX1 in hepatocellular carcinoma (HCC) and elucidate its molecular mechanism.

METHODS

The expression of in HCC tissues and matched adjacent normal tissues ( = 80 cases) was evaluated by immunohistochemistry. Web-based tools UALCAN and the Kaplan-Meier plotter were used to analyze the Cancer Genome Atlas database to compare expression of mRNA to 5-year overall survival. was stably silenced in two HCC cell lines, Hep 3B and Bel-7402, with shRNA technology. An tumorigenesis model was established by subcutaneously injecting sh-APEX1-transfected Bel-7402 cells into mice, and tumor growth was determined. We performed high-throughput transcriptome sequencing in sh-APEX1-treated HCC cells to identify the key KEGG signaling pathways induced by silencing of .

RESULTS

was significantly upregulated and predicted poor clinical overall survival in HCC patients. Silencing inhibited the proliferation of HCC cells and , and it repressed invasion and migration and increased apoptosis and the percentage of cells in G1. Differentially expressed genes upon silencing included genes involved in TNF signaling. A positive correlation between the expression of and was noted, and overexpressing overcame cancer-related phenotypes associated with silencing.

CONCLUSION

enhances the malignant properties of HCC via . may represent a valuable prognostic biomarker and therapeutic target in HCC.