Published online Aug 28, 2019. doi: 10.3748/wjg.v25.i32.4715
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
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.
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.
The aim of this study was to investigate the role of GAS2 in the liver and HCC and its underlying mechanism.
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.
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.
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.
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.