Background
Hepatocellular carcinoma (HCC) is a leading cause of global cancer-related mortality and the most common form of liver cancer. REXO4 (RNA exonuclease 4 homolog) downregulation has previously been linked to enhanced chemosensitivity in breast cancer cells. The present study sought to comprehensively clarify the functional role of REXO4 in HCC.
Conclusions
In summary, these analyses revealed REXO4 to be upregulated in HCC and to be associated with poor patient prognosis. In addition, this gene was closely linked to key cancer hallmark pathways and was revealed to play an important role in the susceptibility of liver tumors to immune cell infiltration and activation. Thus, targeting REXO4 may be a promising approach to treating patients with HCC in the near future.
Methods
REXO4 expression levels in HCC tumor tissues and control tissue samples were established by analyzing data from the Gene Expression Omnibus (GEO) database. The expression of REXO4 was then knocked down in HCC cell lines to explore its functional role in these cells, while a gene set enrichment analysis (GSEA) approach was used to assess the functional regulator network associated with REXO4, and the Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm was used to determine the relationship between this gene and immune cell infiltration of tumor tissues. The relationship between REXO4 and metabolic pathway was analyzed by oil red O staining. Cell Counting Kit-8 assays, colony formation, wound-healing assay, and a nude mouse subcutaneous tumor model were used to evaluate the function of REXO4 in HCC.
Results
REXO4 was highly upregulated in HCC tumors and cell lines, and was an effective predictor of HCC patient prognosis. The results indicated that the knockdown of REXO4 inhibited the proliferation and progression of HCC in vitro and in vivo. GSEA approaches also revealed REXO4 to be associated with tumor progression. Furthermore, REXO4 was associated with the degree of increase of intratumoral immune cell infiltration in HCC tissues and cells, and this gene was also linked with altered lipid metabolism in HCC cells. Conclusions: In summary, these analyses revealed REXO4 to be upregulated in HCC and to be associated with poor patient prognosis. In addition, this gene was closely linked to key cancer hallmark pathways and was revealed to play an important role in the susceptibility of liver tumors to immune cell infiltration and activation. Thus, targeting REXO4 may be a promising approach to treating patients with HCC in the near future.