STEAP4 启动子甲基化与肝细胞癌的肿瘤发生相关。

STEAP4 promoter methylation correlates with tumorigenesis of hepatocellular carcinoma.

作者信息

Tang Yijie, Wang Yingda, Xu Xiaodong, Sun Hongxia, Tang Weidong

机构信息

Department of General Surgery, Nantong Geriatric Rehabilitation Hospital, Nantong, Jiangsu, China; Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

Department of General Surgery, The Second People's Hospital of Jiaxing, China.

出版信息

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

DOI:10.1016/j.prp.2022.153870

PMID:35390632

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.

摘要

背景

本研究旨在寻找参与肝细胞癌（HCC）肿瘤发生过程的有前景的癌症治疗靶点。

方法

通过RNA测序在GSE54503和TCGA数据集中鉴定HCC中的STEAP4。采用qRT-PCR测定STEAP4 mRNA表达水平。通过甲基化特异性PCR（MSP）和亚硫酸氢盐测序法（BSP）检测DNA甲基化。此外，通过体内实验确定STEAP4的肿瘤发生作用。使用去甲基化剂5-氮杂-2'-脱氧胞苷（5-Aza-dC）进一步评估STEAP4对甲基化的作用。