STEAP4 promoter methylation correlates with tumorigenesis of hepatocellular carcinoma.

ABSTRACT

BACKGROUND: The study was aimed to find promising targets for cancer therapy involved in the tumorigenesis of hepatocellular carcinoma (HCC). METHODS: Identification of STEAP4 in HCC between GSE54503 and TCGA datasets by performing RNA-seq. The STEAP4 mRNA expression level was determined by qRT-PCR. DNA methylation was measured by MSP and BSP. Besides, the effect of STEAP4 tumorigenesis was determined by in vivo experiments. The function of STEAP4 on methylation was further assessed by 5-Aza­dC, a demethylating agent. RESULTS: Reduced STEAP4 expression was found in HCC tissues. Promoter region methylation correlated with the downregulated expression of STEAP4. STEAP4 inhibited the proliferation and metastasis of HCC cells. Re-expression of STEAP4 was induced 5-Aza­dC. STEAP4 mediated the biological effects of HCC cells through PI3K/AKT/mTOR pathway inhibition. CONCLUSIONS: Our findings indicate that STEAP4 functions as a suppressor gene in HCC, and hypermethylation is a driving factor in cancer progression.