Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2019; 25(32): 4715-4726
Published online Aug 28, 2019. doi: 10.3748/wjg.v25.i32.4715
Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis
Ran-Xu Zhu, Alfred Sze Lok Cheng, Henry Lik Yuen Chan, Dong-Ye Yang, Wai-Kay Seto
Ran-Xu Zhu, Dong-Ye Yang, Wai-Kay Seto, Department of Gastroenterology and Hepatology, The University of Hong Kong–Shenzhen Hospital, Shenzhen 518053, Guangdong Province, China
Alfred Sze Lok Cheng, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
Henry Lik Yuen Chan, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
Author contributions: Zhu RX and Cheng ASL conceived and designed the study; All authors provided material support; Zhu RX performed the experiments and collected the data; Zhu RX and Cheng ASL analyzed the data; Zhu RX wrote the manuscript; All authors reviewed the manuscript; Zhu RX and Cheng ASL revised the manuscript; Zhu RX and Chan HLY provided financial support; Cheng ASL and Chan HLY provided study supervision; All authors gave final approval of the version of the article to published.
Supported by the National Natural Science Foundation of China, No. 81702777; and Natural Science Foundation of Guangdong Province, No. 2015A030310053.
Institutional review board statement: The study was reviewed and approved by the University of Hong Kong-Shenzhen Hospital Ethics Committee.
Conflict-of-interest statement: No potential conflicts of interest ware disclosed.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Ran-Xu Zhu, MD, PhD, Doctor, Department of Gastroenterology and Hepatology, The University of Hong Kong–Shenzhen Hospital, No. 1 Haiyuan Road, Futian District, Shenzhen 518053, Guangdong Province, China.
Telephone: +86-755-86913333 Fax: +86-755-86913333
Received: March 28, 2019
Peer-review started: March 28, 2019
First decision: April 16, 2019
Revised: July 14, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: August 28, 2019
Research background

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and is a leading cause of cancer-related mortality in China. The prognosis of HCC is poor with high mortality because of limited options of effective treatment. Thus, new therapeutic targets that may confer survival benefit are urgently needed in HCC.

Research motivation

Growth arrest-specific gene 2 (GAS2) is a member of the GAS gene family, which is universally expressed in most normal tissues, particularly in the liver, but is depleted in some tumor tissues. However, the functional mechanisms of GAS2 in HCC are not fully defined.

Research objectives

The aim of this study was to investigate the role of GAS2 in the liver and HCC and its underlying mechanism.

Research methods

GAS2 expression was examined by real-time PCR and western blotting in tissues and cells. The proliferation of GAS2 expression was analyzed by counting, MTS, and colony formation assays. Cell cycle analysis was performed by flow cytometry. Cell apoptosis was investigated by the Annexin V apoptosis assay.

Research results

GAS2 protein expression was more downregulated in HCC than in normal tissues. Overexpression of GAS2 inhibited the proliferation of HCC cells with wild-type p53 and knockdown of GAS2 showed the opposite effects. The more arrested G1 cells in the cell cycle and p53-GAS2 caspase cascade might be involved in the oncogenic function of GAS2 in HCC.

Research conclusions

The study showed that GAS2 suppressed the proliferation and apoptosis of HCC cells, and the possible mechanism was by regulating the cell cycle and p53-dependent apoptosis pathway. Thus, GAS2 is expected to be an important anti-oncogene and potential therapeutic target in HCC.

Research perspectives

The function and mechanism of GAS2 in HCC development has been confirmed, and the significance of GAS2 as a promising therapeutic target for HCC with wild-type p53 is highlighted.