STEAP4 promoter methylation correlates with tumorigenesis of hepatocellular carcinoma

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-Aza-dC, 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-Aza-dC. 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.

Automated summary

This study identified STEAP4 as a tumor suppressor gene in hepatocellular carcinoma (HCC), with its expression regulated by promoter methylation. STEAP4 inhibited the proliferation and metastasis of HCC cells by inhibiting the PI3K/AKT/mTOR pathway. These findings reveal the important role of STEAP4 and methylation regulation in HCC progression.