Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis

Abstract

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.

Genome-wide DNA methylation and gene expression patterns of androgenetic haploid tiger pufferfish (Takifugu rubripes) provide insights into haploid syndrome

“…On the other hand, gas2 and pbrm1 were hypo-methylated in haploid females and males. GAS2 plays an important role in mitogenesis, cell cycle, microfilament alterations and cellular morphological variation during apoptosis 35 – 37 . pbrm1 gene encodes BAF180 protein, which is a subunit of the ATP‐dependent complex SWItch/Sucrose NonFermentable (SWI/SNF) regulating chromatin remodeling 38 .…”

The Association of an SNP in the EXOC4 Gene and Reproductive Traits Suggests Its Use as a Breeding Marker in Pigs

“…P53 participates in maintaining cell growth [ 34 ]. P53 can enhance stability through phosphorylation and the activation or inhibition of the transcription of downstream genes, thus inducing cell cycle arrest and apoptosis [ 35 ]. ELK1 is a transcription factor belonging to the ETS oncogene family and induces endothelial-to-myofibroblast transition of tumor endothelial cells [ 36 ], which plays an important role in breast and ovarian cancers [ 15 ].…”

miR-520c-3p regulates IL-1β-stimulated human chondrocyte apoptosis and cartilage degradation by targeting GAS2

“…Recently, Kong et al [ 21 ] found that GAS2 promotes cell proliferation and invasion and suppresses apoptosis in pediatric T-cell acute lymphoblastic leukemia and activates Wnt/β-Catenin pathway. Zhu et al [ 22 ] also found that GAS2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis. In this study, GAS2 was initially measured by RT-PCR and was upregulated in OA-affected cartilage and IL-1β-treated chondrocytes.…”