STEAP4 promoter methylation correlates with tumorigenesis of hepatocellular carcinoma

Pathol Res Pract. 2022 May:233:153870. doi: 10.1016/j.prp.2022.153870. Epub 2022 Apr 1.

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-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.

Keywords: Hepatocellular carcinoma; Methylation; Progression; STEAP4.

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Cell Transformation, Neoplastic / genetics
  • DNA Methylation / genetics
  • Humans
  • Liver Neoplasms* / pathology
  • Membrane Proteins / metabolism
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Promoter Regions, Genetic / genetics

Substances

  • Membrane Proteins
  • Oxidoreductases
  • STEAP4 protein, human