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Updated: Sep 27, 2025

Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
STEAP4 promoter methylation correlates with tumorigenesis of hepatocellular carcinoma
Yijie Tang1, Yingda Wang2, Xiaodong Xu3
1Department of General Surgery, Nantong Geriatric Rehabilitation Hospital, Nantong, Jiangsu, China; Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
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.
Insights
STEAP4 acts as a tumor suppressor in hepatocellular carcinoma (HCC). Its reduced expression, driven by promoter hypermethylation, inhibits cancer cell proliferation and metastasis, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Hepatocellular carcinoma (HCC) tumorigenesis requires novel therapeutic targets.
- Identifying key genes in HCC development is crucial for effective cancer therapy.
Purpose of the Study:
- To investigate the role of STEAP4 in hepatocellular carcinoma (HCC) development.
- To determine if STEAP4 functions as a tumor suppressor or oncogene in HCC.
- To explore the regulatory mechanisms, including DNA methylation, controlling STEAP4 expression in HCC.
Main Methods:
- RNA sequencing (RNA-seq) on GSE54503 and TCGA datasets to identify STEAP4.
- Quantitative real-time PCR (qRT-PCR) to measure STEAP4 mRNA levels.
- Methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) to assess DNA methylation.
- In vivo experiments to evaluate STEAP4's effect on tumorigenesis.
- Treatment with 5-aza-2'-deoxycytidine (5-Aza-dC), a demethylating agent, to study methylation's functional impact.
Main Results:
- STEAP4 expression was significantly reduced in HCC tissues compared to normal tissues.
- Promoter region hypermethylation was strongly correlated with the downregulation of STEAP4 mRNA.
- Overexpression of STEAP4 suppressed HCC cell proliferation and metastasis in vitro and in vivo.
- Demethylation using 5-Aza-dC treatment led to the re-expression of STEAP4.
- STEAP4 exerted its tumor-suppressive effects by inhibiting the PI3K/AKT/mTOR signaling pathway.
Conclusions:
- STEAP4 functions as a tumor suppressor gene in hepatocellular carcinoma.
- Hypermethylation of the STEAP4 promoter is a key mechanism driving its downregulation and contributing to HCC progression.
- Targeting STEAP4 or demethylation pathways may represent a novel therapeutic strategy for HCC.
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