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Updated: Jan 19, 2026
Generation and Isolation of Cell Cycle-arrested Cells with Complex Karyotypes
Published on: April 13, 2018
Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent
Ran-Xu Zhu1, Alfred Sze Lok Cheng2, Henry Lik Yuen Chan3
1Department of Gastroenterology and Hepatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, Guangdong Province, China. zhurx@hku-szh.org.
Background:
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.
Aim:
To investigate the function and mechanism of GAS2 in HCC.
Methods:
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.
Results:
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).
Conclusion:
GAS2 plays a vital role in HCC cell proliferation and apoptosis, possibly by regulating the cell cycle and p53-dependent apoptosis pathway.
Insights
Growth arrest-specific gene 2 (GAS2) is downregulated in hepatocellular carcinoma (HCC), inhibiting tumor cell proliferation and promoting apoptosis. GAS2 regulates the cell cycle and p53-dependent apoptosis, offering potential therapeutic targets for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Growth arrest-specific gene 2 (GAS2) modulates cell cycle, apoptosis, and survival.
- GAS2 is expressed in normal tissues but depleted in some tumors, with its role in hepatocellular carcinoma (HCC) unclear.
Purpose of the Study:
- To investigate the function and molecular mechanisms of GAS2 in HCC.
Main Methods:
- Analyzed GAS2 expression in HCC and normal tissues using real-time PCR and western blotting.
- Assessed cell proliferation, cell cycle, and apoptosis in HCC cells with altered GAS2 levels.
- Investigated the role of p53 in GAS2-mediated apoptosis.
Main Results:
- GAS2 expression was significantly lower in HCC tissues compared to normal tissues.
- GAS2 overexpression inhibited HCC cell proliferation and induced G1 cell cycle arrest and apoptosis.
- GAS2-induced apoptosis was dependent on p53, with GAS2 upregulation enhancing p53 and apoptosis marker expression.
Conclusions:
- GAS2 plays a critical role in regulating HCC cell proliferation and apoptosis.
- GAS2 may function by modulating the cell cycle and activating the p53-dependent apoptosis pathway.
- GAS2 represents a potential therapeutic target for HCC treatment.
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