BTG2 Is Down-Regulated and Inhibits Cancer Stem Cell-Like Features of Side Population Cells in Hepatocellular Carcinoma
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Our previous study found that B cell translocation gene 2 (BTG2) was hyper-methylated and down-regulated in side population (SP) cells of hepatocellular carcinoma (HCC) cell line. However, its clinical significances and biological impacts on HCC SP cells remained unclear.
To investigate the prognostic value of BTG2 gene in HCC and its influences on cancer stem cells (CSCs)-like traits of HCC cell line SP cells.
BTG2 expression in human HCC and adjacent non-cancerous tissues was detected by immunohistochemical staining and quantitative real-time PCR, and also obtained from GEO and TCGA data. Its prognostic values were assessed. Its biological influences on HCC cell line SP cells were evaluated using cell viability, cell cycle, plate clone-forming assay, and chemoresistance in vitro and tumorigenicity in vivo.
BTG2 expression was significantly suppressed in human HCC compared to adjacent non-cancerous tissues. BTG2 expression was correlated with TNM stage, tumor size and vascular invasion. Lower expression of BTG2 was associated with poorer overall survival and disease-free survival. In vitro, overexpression of BTG2 substantially suppressed cell proliferation and accumulation of HCC cell line SP cells in G0/G1 phase. Colony formation ability was markedly suppressed by BTG2 overexpression. Moreover, sensitivity of HCC cell line SP cells to 5-fluorouracil was substantially increased by overexpression of BTG2. Furthermore, tumorigenicity of HCC cell line SP cells transfected with BTG2 plasmids was significantly reduced in vivo.
BTG2 gene could regulate the CSC-like traits of HCC cell line SP cells, and it represented as a molecular prognostic marker for HCC.
KeywordsB cell translocation gene 2 Side population cells Hepatocellular carcinoma Cancer stem cell
This study was supported by the National Natural Science Foundation of China (No. 81472261), the Natural Science Foundation of Guangdong Province (No. 2015A030313032), the Science and Technology Development Projects of Guangdong Province, China (No. 2013B021800122), the Science and Technology Development Projects of Guangzhou, Guangdong, China (No. 201604020044).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 6.Boiko AD, Porteous S, Razorenova OV, Krivokrysenko VI, Williams BR, Gudkov AV. A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation. Genes Dev. 2006;20:236–252.CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Chen Y, Chen C, Zhang Z, et al. Expression of B-cell translocation gene 2 is associated with favorable prognosis in hepatocellular carcinoma patients and sensitizes irradiation-induced hepatocellular carcinoma cell apoptosis in vitro and in nude mice. Oncol Lett. 2017;13:2366–2372.PubMedPubMedCentralGoogle Scholar