c-Jun-dependent β3GnT8 promotes tumorigenesis and metastasis of hepatocellular carcinoma by inducing CD147 glycosylation and altering N-glycan patterns
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Chunliang Liu1,*, Hao Qiu1,*, Dandan Lin1, Zerong Wang2, Ning Shi3, Zengqi Tan4, Jun Liu1, Zhi Jiang1 and Shiliang Wu1
1Department of Biochemistry and Molecular Biology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu 215123, P.R. China
2Department of Infectious Diseases, The Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu 215007, P.R. China
3Department of Physiology and Pharmacology, University of Georgia, Athens 30602 GA, USA
4College of Life Science, Northwest University, Xian, Shanxi 710069, P.R. China
*These authors contributed equally to this work
Shiliang Wu, email: [email protected]
Zhi Jiang, email: [email protected]
Keywords: β3GnT8; hepatocellular carcinoma; CD147; tumorigenesis; glycosylation
Received: September 07, 2017 Accepted: December 01, 2017 Epub: January 12, 2018 Published: April 06, 2018
β3GnT8, a key polylactosamine synthase, plays a vital role in progression of various types of human cancer. The role of β3GnT8 in hepatocellular carcinoma (HCC) and the underlying mechanisms, however, remain largely unknown. In this study, we found that β3GnT8 and polylactosamine were highly expressed in HCC tissues compared with those in adjacent paracancer tissues. Overexpression of β3GnT8 promoted while knockdown of β3GnT8 inhibited HCC cell invasion and migration in vitro. Importantly, enhanced tumorigenesis was observed in nude mice inoculated with β3GnT8-overexpressing HCC cells, suggesting that β3GnT8 is important for HCC development in vitro and in vivo. Mechanistically, β3GnT8 modulated the N-glycosylation patterns of CD147 and altered the polylactosamine structures in HCC cells by physically interacting with CD147. In addition, our data showed the c-Jun could directly bind to the promoter of β3GnT8 gene and regulate β3GnT8 expression. β3GnT8 regulated HCC cell invasion and migration in a C-Jun-dependent manner. Collectively, our study identified β3GnT8 as a novel regulator for HCC invasion and tumorigenesis. Targeting β3GnT8 may be a potential therapeutic strategy against HCC.
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