Monoacylglycerol lipase promotes progression of hepatocellular carcinoma via NF-κB-mediated epithelial-mesenchymal transition

• DOI: 10.1186/s13045-016-0361-3
• Publication Date: 2016-11-24T19:50:11Z
• Authors: Weiping Zhu; Yiming Zhao; Jiamin Zhou; Xin Wang; Qi Pan; Ning Zhang; Longrong Wang; Miao Wang; Dihua Zhan; Zeyang Liu; Xigan He; Dening Ma; Shuang Liu; Lu Wang
• Keywords: Male; Cancer Research; Carcinoma, Hepatocellular; Epithelial-Mesenchymal Transition; Hepatocellular carcinoma; Gene Expression; NF-κB; 03 medical and health sciences; Biomarkers, Tumor; Humans; Diseases of the blood and blood-forming organs; Neoplasm Invasiveness; Molecular Biology; RC254-282; Cell Proliferation; 0303 health sciences; Research; Liver Neoplasms; EMT; NF-kappa B; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Hematology; Middle Aged; Prognosis; Monoacylglycerol Lipases; 3. Good health; Oncology; Tissue Array Analysis; MAGL; Disease Progression; Female; RC633-647.5

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 MAGLhigh group was markedly poorer than that for the MAGLlow group 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.