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
Processing time: 153 Days and 21.4 Hours
Growth arrest-specific gene 2 (GAS2) plays a role in modulating in reversible growth arrest cell cycle, apoptosis, and cell survival. GAS2 protein 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 hepatocellular carcinoma (HCC) are not fully defined.
To investigate the function and mechanism of GAS2 in HCC.
GAS2 expression in clinic liver and HCC specimens was analyzed by real-time PCR and western blotting. Cell proliferation was analyzed by counting, MTS, and colony formation assays. Cell cycle analysis was performed by flow cytometry. Cell apoptosis was investigated by Annexin V apoptosis assay and western blotting.
GAS2 protein expression was lower in HCC than in normal tissues. Overexpression of GAS2 inhibited the proliferation of HCC cells with wide-type p53, while knockdown of GAS2 promoted the proliferation of hepatocytes (P < 0.05). Furthermore, GAS2 overexpression impeded the G1-to-S cell cycle transition and arrested more G1 cells, particularly the elevation of sub G1 (P < 0.01). Apoptosis induced by GAS2 was dependent on p53, which was increased by etoposide addition. The expression of p53 and apoptosis markers was further enhanced when GAS2 was upregulated, but became diminished upon downregulation of GAS2. In the clinic specimen, GAS2 was downregulated in more than 60% of HCCs. The average fold changes of GAS2 expression in tumor tissues were significantly lower than those in paired non-tumor tissues (P < 0.05).
GAS2 plays a vital role in HCC cell proliferation and apoptosis, possibly by regulating the cell cycle and p53-dependent apoptosis pathway.
Core tip: This study elucidated the function and mechanism of growth arrest-specific gene 2 (GAS2) in hepatocellular carcinoma (HCC) progression. By overexpression and knockdown approaches, we found that GAS2 inhibited the proliferation of HCC with wild-type p53. The effects of GAS2 on the cell cycle and apoptosis were investigated by flow cytometry, Annexin V apoptosis, and western blot assay, respectively. GAS2 suppressed HCC proliferation by deregulating the cell cycle and p53-dependent apoptosis pathway. Thus, GAS2 is expected to be a promising anti-oncogene and potential therapeutic target in HCC with wild-type p53.