Department of Gastroenterology and Hepatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, Guangdong Province, China.
School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
World J Gastroenterol. 2019 Aug 28;25(32):4715-4726. doi: 10.3748/wjg.v25.i32.4715.
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 ( < 0.05). Furthermore, GAS2 overexpression impeded the G1-to-S cell cycle transition and arrested more G1 cells, particularly the elevation of sub G1 ( < 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 ( < 0.05).
GAS2 plays a vital role in HCC cell proliferation and apoptosis, possibly by regulating the cell cycle and p53-dependent apoptosis pathway.
生长停滞特异性基因 2（GAS2）在调节可逆性生长停滞细胞周期、细胞凋亡和细胞存活方面发挥作用。GAS2 蛋白在大多数正常组织中普遍表达，尤其是在肝脏中，但在一些肿瘤组织中缺失。然而，GAS2 在肝细胞癌（HCC）中的功能机制尚未完全确定。
研究 GAS2 在 HCC 中的作用和机制。
通过实时 PCR 和 Western blot 分析临床肝脏和 HCC 标本中的 GAS2 表达。通过计数、MTS 和集落形成测定分析细胞增殖。通过流式细胞术进行细胞周期分析。通过 Annexin V 凋亡测定和 Western blot 研究细胞凋亡。
GAS2 蛋白在 HCC 中的表达低于正常组织。GAS2 的过表达抑制了具有野生型 p53 的 HCC 细胞的增殖，而 GAS2 的敲低促进了肝细胞的增殖（<0.05）。此外，GAS2 过表达阻碍了 G1 期到 S 期的细胞周期转换，并使更多的 G1 期细胞停滞，特别是亚 G1 期的升高（<0.01）。GAS2 诱导的细胞凋亡依赖于 p53，加入依托泊苷可增加 p53 的表达。上调 GAS2 可进一步增强 p53 及其凋亡标志物的表达，但下调 GAS2 可使其表达减弱。在临床标本中，超过 60%的 HCC 中 GAS2 下调。肿瘤组织中 GAS2 表达的平均倍数变化明显低于配对非肿瘤组织（<0.05）。
GAS2 在 HCC 细胞增殖和凋亡中发挥重要作用，可能通过调节细胞周期和 p53 依赖性凋亡途径。
