BCLB, methylated in hepatocellular carcinoma, is a starvation stress sensor that induces apoptosis and autophagy through the AMPK-mTOR signaling cascade
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AbstractEpigenetic disruption of tumor suppressor genes (TSGs), particularly DNA methylation, plays a key role in hepatocellular carcinoma (HCC) pathogenesis. Through methylome study, we identified BCLB as a methylated gene in HCC. BCLB was methylated in all tumor cell lines with silenced or reduced expression. BCLB was further found to be silenced in 55.2% (58/105) of HCC samples, while 91.4% (96/105) of paired non-tumor tissues showed high BCLB expression. BCLB protein expression was significantly correlated with HBV status (p = 0.036), AFP (p = 0.048), tumor size (p = 0.006), and TNM stage (p = 0.022). The overall survival and disease-free survival rate of HCC patients with positive BCLB expression were both significantly higher than those with negative BCLB expression (p = 0.032 and 0.027, respectively). Ectopic expression of BCLB in HCC cells inhibited cell growth in vitro and in vivo. Mechanistic study showed that BCLB expression was a starvation stress sensor inducing apoptosis and autophagy simultaneously in HCC cells through the adenosine monophosphate-activated protein kinase AMPK-mTOR signaling cascade. Thus, epigenetic suppression of BCLB expression is involved in HCC development, which might have therapeutic implications for HCC patients. (C) 2017 Elsevier B.V. All rights reserved.
All Author(s) ListLiu XL, Hu XT, Kuang YY, Yan PJ, Li LL, Li C, Tao Q, Cai XJ
Journal nameCancer Letters
Year2017
Month6
Volume Number395
PublisherELSEVIER IRELAND LTD
Pages63 - 71
ISSN0304-3835
eISSN1872-7980
LanguagesEnglish-United Kingdom
KeywordsBCLB,Tumor suppressor gene,Methylation,Apoptosis,Autophagy
Web of Science Subject CategoriesOncology;Oncology

Last updated on 2020-23-11 at 01:37