c-Jun-dependent β3GnT8 promotes tumorigenesis and metastasis of hepatocellular carcinoma by inducing CD147 glycosylation and altering N-glycan patterns

// Chunliang Liu 1, * , Hao Qiu 1, * , Dandan Lin 1 , Zerong Wang 2 , Ning Shi 3 , Zengqi Tan 4 , Jun Liu 1 , Zhi Jiang 1 and Shiliang Wu 1 1 Department of Biochemistry and Molecular Biology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu 215123, P.R. China 2 Department of Infectious Diseases, The Fifth People’s Hospital of Suzhou, Jiangsu 215007, P.R. China 3 Department of Physiology and Pharmacology, University of Georgia, Athens 30602 GA, USA 4 College of Life Science, Northwest University, Xian, Shanxi 710069, P.R. China * These authors contributed equally to this work Correspondence to: Shiliang Wu, email: shiliang_wu@126.com Zhi Jiang, email: jiangzhi@suda.edu.cn Keywords: β3GnT8; hepatocellular carcinoma; CD147; tumorigenesis; glycosylation Received: September 07, 2017      Accepted: December 01, 2017      Epub: January 12, 2018      Published: April 06, 2018 ABSTRACT 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.