title: Monoacylglycerol Lipase: A Novel Potential Therapeutic Target and Prognostic Indicator for Hepatocellular Carcinoma.
abstract: Monoacylglycerol lipase (MAGL) is a key enzyme in lipid metabolism that is demonstrated to be involved in tumor progression through both energy supply of fatty acid (FA) oxidation and enhancing cancer cell malignance. The aim of this study was to investigate whether MAGL could be a potential therapeutic target and prognostic indicator for hepatocellular carcinoma (HCC). To evaluate the relationship between MAGL levels and clinical characteristics, a tissue microarray (TMA) of 353 human HCC samples was performed. MAGL levels in HCC samples were closely linked to the degree of malignancy and patient prognosis. RNA interference, specific pharmacological inhibitor JZL-184 and gene knock-in of MAGL were utilized to investigate the effects of MAGL on HCC cell proliferation, apoptosis, and invasion. MAGL played important roles in both proliferation and invasion of HCC cells through mechanisms that involved prostaglandin E2 (PGE2) and lysophosphatidic acid (LPA). JZL-184 administration significantly inhibited tumor growth in mice. Furthermore, we confirmed that promoter methylation of large tumor suppressor kinase 1 (LATS1) resulted in dysfunction of the Hippo signal pathway, which induced overexpression of MAGL in HCC. These results indicate that MAGL could be a potentially novel therapeutic target and prognostic indicator for HCC.
authors: The Second Affiliated Hospital of Chongqing Medical University, department of Urinary Surgery, Chongqing City, 400010, China.
authors: Junyong
authors: J
authors: Zhang
authors: The Second Affiliated Hospital of Chongqing Medical University, department of Hepatobiliary Surgery, Chongqing City, 400010, China.
authors: Zuojin
authors: Z
authors: Liu
authors: McMaster University, department of Clinical Epidemiology and Biostatistics and Population Health Research Institution, Hamilton, Ontario, L8S4L8, Canada.
authors: Zhengrong
authors: Z
authors: Lian
authors: The First Affiliated Hospital of Chongqing Medical University, department of Hepatobiliary Surgery, Chongqing City, 400016, China.
authors: Rui
authors: R
authors: Liao
authors: The Second Affiliated Hospital of Chongqing Medical University, department of Hepatobiliary Surgery, Chongqing City, 400010, China.
authors: Yi
authors: Y
authors: Chen
authors: The Second Affiliated Hospital of Chongqing Medical University, department of Hepatobiliary Surgery, Chongqing City, 400010, China.
authors: Yi
authors: Y
authors: Qin
authors: Fuling Center Hospital, department of Emergency medicine, Fuling District, Chongqing, 408000, China.
authors: Jinlong
authors: J
authors: Wang
authors: The Second Affiliated Hospital of Chongqing Medical University, department of Urinary Surgery, Chongqing City, 400010, China.
authors: Qing
authors: Q
authors: Jiang
authors: Fuling Center Hospital, department of Hepatobiliary Surgery, Fuling District, Chongqing, 408000, China.
authors: Xiaobo
authors: X
authors: Wang
authors: The Second Affiliated Hospital of Chongqing Medical University, department of Hepatobiliary Surgery, Chongqing City, 400010, China.
authors: Jianping
authors: J
authors: Gong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D052117:Benzodioxoles / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D056945:Hep G2 Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010880:Piperidines / Q000494:pharmacology; D011379:Prognosis; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D052117:Benzodioxoles; D004791:Enzyme Inhibitors; C534333:JZL 184; D010880:Piperidines; C092745:LATS1 protein, human; D017346:Protein Serine-Threonine Kinases; D008994:Monoacylglycerol Lipases