title: Monoacylglycerol lipase promotes progression of hepatocellular carcinoma via NF-κB-mediated epithelial-mesenchymal transition.
abstract: Monoacylglycerol lipase (MAGL), a critical lipolytic enzyme, has emerged as a key regulator of tumor progression, yet its biological function and clinical significance in hepatocellular carcinoma (HCC) is still unknown.
  
  
  
  In this study, we used a tissue microarray containing samples from 170 HCC patients to evaluate the expression of MAGL and its correlation with other clinicopathologic characteristics. In addition, we investigated the regulating effects of MAGL on various HCC lines. Finally, we identified the NF-κB signaling pathway participated in MAGL-mediated epithelial-mesenchymal transition (EMT) using HCC cell lines with different metastatic potentials.
  
  
  
  The expression of MAGL was significantly higher in HCC tumors than in matched peritumor tissues. Specifically, high MAGL expression was found in tumors with larger tumor size, microvascular invasion, poor differentiation, or advanced TNM stage. In addition, the clinical prognosis for the MAGLhighgroup was markedly poorer than that for the MAGLlowgroup in the 1-, 3-, and 5-year overall survival times and recurrence rates of HCC patients. MAGL expression was an independent prognostic factor for both survival and recurrence after curative resection. Furthermore, the upregulation of MAGL in HCC cells promoted cell growth and invasiveness abilities, and accompanied by EMT. In contrast, downregulation of MAGL obviously inhibited these characteristics. Moreover, further investigations verified that MAGL facilitates HCC progression via NF-κB-mediated EMT process.
  
  
  
  Our findings demonstrate MAGL could promote HCC progression by the induction of EMT and suggest a potential therapeutic target, as well as a biomarker for prognosis, in patients with HCC.
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Rheumatology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, 1 Xiyuan Caochang, Haidian District, Beijing, 100091, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Longrong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Dihua
authors.initials: D
authors.lastname: Zhan
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Zeyang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Xigan
authors.initials: X
authors.lastname: He
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Dening
authors.initials: D
authors.lastname: Ma
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China. wang.lu99@hotmail.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008994:Monoacylglycerol Lipases / Q000032:analysis / Q000235:genetics*; D016328:NF-kappa B / Q000502:physiology*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D016328:NF-kappa B; D008994:Monoacylglycerol Lipases
keywords: EMT; Hepatocellular carcinoma; MAGL; NF-κB