Abstract
BackgroundBTG3 (B-cell translocation gene 3) has been identified as a tumor suppressor and hypermethylation contributes to its down-regulation in some tumors, but its role in hepatocellular carcinoma (HCC) remain unknown. This study aimed to detect the expression and methylation status of BTG3 in HCC cell lines or tissues, and determine its function in HCC progression.MethodologyThe expression of BTG3 was detected in HCC cell lines and HCC tissue by real-time RT-PCR, Western blot or immunohistochemistry. The promoter methylation status of BTG3 was measured by using methylation-specific PCR in HCC cell lines. A series of assays were performed to evaluate the effect of BTG3 on proliferation, invasion and cell cycle transition in vitro. ResultsBTG3 expression was lower in HCC cell lines than in hepatocyte cell line LO2 (P<0.05). BTG3 was also down-regulated in HCC tissues. Its expression was positively correlated with differentiation and distant metastasis (P<0.05). Patients with lower BTG3 expression had shorter overall survival time (P=0.029). DNA methylation directed repression of BTG3 mRNA expression in HCC cell lines. BTG3 suppressed proliferation, invasion and induces G1/S cycle arrest of HCC cells in vitro. ConclusionDown-regulation of BTG3 due to the promoter hypermethylation is closely associated with proliferation, invasion and cell cycle arrest of HCC cells. It may be a novel prognostic biomarker for HCC patients.
Highlights
Primary hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide in terms of numbers of cases of 626,000, and the third most common cause of death from cancer (598,000 deaths annually)[1]
B-cell translocation gene 3 (BTG3) expression was lower in HCC cell lines than in hepatocyte cell line LO2 (P
BTG3 was down-regulated in HCC tissues
Summary
Primary hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide in terms of numbers of cases of 626,000, and the third most common cause of death from cancer (598,000 deaths annually)[1]. B-cell translocation gene 3 (BTG3) belongs to an antiproliferative B-cell translocation gene/Transducer of ErbB2 (BTG/Tob) gene family, which includes BTG1, BTG2/ TIS21/PC3, Tob, Tob and PC3b in human cells[3]. These proteins all contain two short conserved domains in their Nterminal part (box A and box B), separated by a spacer sequence of 20-25 non-conserved amino acids[3,4,5]. BTG3 (B-cell translocation gene 3) has been identified as a tumor suppressor and hypermethylation contributes to its down-regulation in some tumors, but its role in hepatocellular carcinoma (HCC) remain unknown. This study aimed to detect the expression and methylation status of BTG3 in HCC cell lines or tissues, and determine its function in HCC progression
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