The Suppressive Role and Aberrent Promoter Methylation of BTG3 in the Progression of Hepatocellular Carcinoma

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.

Down-regulation of BTG3 promotes cell proliferation, migration and invasion and predicts survival in gastric cancer

“…In addition, we demonstrated that BTG3 obviously decreased the migratory and invasive abilities of GC cells in vitro. Decreased expression of BTG3 is linked to carcinogenesis and aggressiveness of ovarian cancer and hepatocellular cancer (Lv et al 2013;Deng et al 2013). Therefore, the above results provide evidence that BTG3 can function as a suppressor in the progression of GC.…”

“…Recently, several studies have shown that BTG3 was associated with tumorigenesis. It has been reported as a tumor suppressor in several tumor types (Majid et al 2009(Majid et al , 2010Yu et al 2008;Lv et al 2013;Chen et al 2013). However, the expression pattern and function of BTG3 in the progression of GC remain elusive.…”

“…Our results clearly showed that BTG3 expression was significantly down-regulated in GC tissues or lymphatic metastatic tissues. Aberrant epigenetic regulation of BTG3 promoter, such as by DNA hypermethylation and/or histone modification, may represent a key mechanism of down-regulation of BTG3 in renal cancer, prostate cancer and several human cancers (Majid et al 2009(Majid et al , 2010Yu et al 2008;Lv et al 2013). Moreover, BTG3 expression was correlated strongly with distant metastasis, suggesting that BTG3 may be associated with the progression of GC.…”

MiR-106b-5p Promotes Proliferation and Inhibits Apoptosis by Regulating BTG3 in Non-Small Cell Lung Cancer

“…Some evidence has shown that BTG3 expression is associated with tumorigenesis and serves as a candidate tumor suppressor gene in various cancers [45-47]. As reported, BTG3 involves in the suppression of proliferation, cell cycle progression and metastasis [48-51]. However, the association between BTG3 and miRNA has rarely been reported.…”

Direct Downregulation of B-Cell Translocation Gene 3 by microRNA-93 Is Required for Desensitizing Esophageal Cancer to Radiotherapy

“…These results strongly suggest that miR-93 directly binds to the predicted BTG3 3 0 -UTR site and accelerates BTG3 mRNA degradation. Of note, the observed downregulation of BTG3 in ESC may only cause in part by miR-93, as the promoter region of BTG3 is known to be hypermethylated in several human cancers, which also contributes to downregulation of BTG mRNA [23][24][25][26].…”