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

Published on 2018-05-15T05:00:00Z (GMT) by
Abstract Background 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. Methods 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. Results 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/PPARÎą signaling. Conclusion Our results reveal that NEAT1-modulates abnormal lipolysis via ATGL to drive HCC proliferation.

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Liu, Xirui; Liang, Yingjian; Song, Ruipeng; Yang, Guangchao; Han, Jihua; Lan, Yaliang; Pan, Shangha; Zhu, Mingxi; Liu, Yao; Wang, Yan; Meng, Fanzheng; Cui, Yifeng; Wang, Jiabei; Zhang, Bo; Song, Xuan; Lu, Zhaoyang; Zheng, Tongsen; Liu, Lianxin (2018): Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation. figshare. Collection.