Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation

• DOI: 10.1186/s12943-018-0838-5
• Publication Date: 2018-05-15T14:26:56Z
• Authors: Xirui Liu; Yingjian Liang; Ruipeng Song; Guangchao Yang; Jihua Han; Yaliang Lan; Shangha Pan; Mingxi Zhu; Yao Liu; Yan Wang; Fanzheng Meng; Yifeng Cui; Jiabei Wang; Bo Zhang; Xuan Song; Zhaoyang Lu; Tongsen Zheng; Lianxin Liu
• Keywords: Male; 0301 basic medicine; Carcinoma, Hepatocellular; Hepatocellular carcinoma; Lipolysis; NEAT1; Fatty Acids, Nonesterified; Diglycerides; Mice; 03 medical and health sciences; Cell Line, Tumor; ATGL/PNPLA2; Animals; Humans; RC254-282; Cell Proliferation; Research; Liver Neoplasms; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Hep G2 Cells; Lipase; LncRNA; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; Female; RNA, Long Noncoding; Lipid metablosim; Neoplasm Transplantation

Abnormal metabolism, including abnormal lipid metabolism, is a hallmark of cancer cells. Some studies have demonstrated that the lipogenic pathway might promote the development of hepatocellular carcinoma (HCC). However, the role of the lipolytic pathway in HCC has not been elucidated.We compared levels of adipose triglyceride lipase (ATGL) in human HCC and healthy liver tissues by real time PCR, western blot and immunohistochemistry. We measured diacylglycerol(DAG) and free fatty acid (FFA) levels in HCC cells driven by the NEAT1-ATGL axis and in HCC tissues. We also assessed the effects of ATGL, DAG, FFA, and NEAT1 on HCC cells proliferation in vitro and in an orthotopic xenograft HCC mouse model. We also performed a luciferase reporter assay to investigate the interaction between NEAT1/ATGL and miR-124-3p.We found that the lipolytic enzyme, ATGL is highly expressed in human HCC tissues and predicts poor prognosis. We also found that high levels of DAG and FFA are present in HCC tissues. Furthermore, the lncRNA-NEAT1 was found to modulate ATGL expression and disrupt lipolysis in HCC cells via ATGL. Notably, ATGL and its products, DAG and FFA, were shown to be responsible for NEAT1-mediated HCC cell growth. NEAT1 regulated ATGL expression by binding miR-124-3p. Additionally, NEAT1 knockdown attenuated HCC cell growth through miR-124-3p/ATGL/DAG+FFA/PPARα signaling.Our results reveal that NEAT1-modulates abnormal lipolysis via ATGL to drive HCC proliferation.