Affordable Access

deepdyve-link
Publisher Website

ACADS acts as a potential methylation biomarker associated with the proliferation and metastasis of hepatocellular carcinomas.

Authors
  • Chen, Diyu1, 2
  • Feng, Xiaode1
  • Lv, Zhen1
  • Xu, Xiaofeng1
  • Lu, Yuejie1
  • Wu, Wenxuan1
  • Wu, Hao1
  • Liu, Hua1
  • Cao, Linping1
  • Ye, Sunyi3
  • Chen, Jianzhong2
  • Wu, Jian1
  • 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China. , (China)
  • 2 , Institute of Immunology School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang, China. , (China)
  • 3 , Department of urology, The first affiliated hospital, school of medicine, Zhejiang University, Hangzhou, 310058, Zhejiang, China. , (China)
Type
Published Article
Journal
Aging
Publisher
"Impact Journals, LLC "
Publication Date
Oct 25, 2019
Volume
11
Identifiers
DOI: 10.18632/aging.102292
PMID: 31652420
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Hepatocellular carcinomas (HCC) constantly rank among the malignancies with the highest death tolls on the global scale. Moreover, HCC are associated with a limited set of therapeutic options. This is particularly true in the case of advanced stage cancers, where long-term survival is uncommon. For the inoperable, advanced HCC patients, chemotherapy is the main modality of treatment. Due to the lack of known molecular targets, the efficacy of the chemotherapy is limited. These findings clearly indicate that DNA methylation plays a key role in regulating ACADS expression and that it can be a potential therapeutic target for treating HCC. A thorough comparative analysis of 282 cancer samples with 47 normal samples from GEO datasets resulted in the observation that that the level of ACADS was significantly downregulated in HCC. Loss-of-function analyses were then conducted to understand the biological function of ACADS in HCC. It was noted that ACADS was involved in the proliferation and metastasis of HCC. Experiments involving the knockdown of DMNT expression led to the discovery that the expression of ACADS in the HCC cells was significantly increased. The TCGA database was then employed to identify tumor tissue samples which showed higher methylation levels at cg01535453, cg08618068, and cg10174836 (which are the target sites of the ACADS CpG islands) as compared with normal liver tissue samples. All these findings indicated that ACADS might be a novel methylation biomarker associated with HCC.

Report this publication

Statistics

Seen <100 times