Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation.
Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation.
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长非编码 RNA NEAT1 通过 ATGL 调节异常脂肪分解驱动肝细胞癌增殖。
DOI：
10.1186/s12943-018-0838-5
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发表时间：
2018-05-15
期刊：
影响因子：
37.3
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Liu X;Liang Y;Song R;Yang G;Han J;Lan Y;Pan S;Zhu M;Liu Y;Wang Y;Meng F;Cui Y;Wang J;Zhang B;Song X;Lu Z;Zheng T;Liu L
代谢异常，包括脂质代谢异常，是癌细胞的标志。有研究表明，脂肪生成途径可能促进肝细胞癌（HCC）的发生发展。然而，脂肪分解途径在HCC中的作用尚未阐明。我们采用真实的时间PCR、免疫印迹和免疫组化方法比较了脂肪甘油三酯脂肪酶（ATGL）在人肝癌和健康肝组织中的表达水平。我们测量了由NEAT 1-ATGL轴驱动的HCC细胞和HCC组织中的二酰基甘油（DAG）和游离脂肪酸（FFA）水平。我们还评估了ATGL、DAG、FFA和NEAT 1在体外和原位异种移植HCC小鼠模型中对HCC细胞增殖的影响。我们还进行了荧光素酶报告基因测定以研究NEAT 1/ATGL和miR-124- 3 p之间的相互作用。我们发现脂肪分解酶ATGL在人肝癌组织中高度表达，并预测预后不良。我们还发现高水平的DAG和FFA存在于HCC组织中。此外，发现lncRNA-NEAT 1调节ATGL表达并通过ATGL破坏HCC细胞中的脂解。值得注意的是，ATGL及其产物DAG和FFA被证明是NEAT 1介导的HCC细胞生长的原因。NEAT 1通过与miR-124- 3 p结合调节ATGL表达。此外，NEAT 1敲低通过miR-124- 3 p/ATGL/DAG+FFA/PPARα信号转导减弱HCC细胞生长。我们的研究结果表明，NEAT 1-调节异常脂肪分解通过ATGL驱动肝癌增殖。本文的在线版本（10.1186/s12943-018-0838-5）包含补充材料，可供授权用户使用。
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. The online version of this article (10.1186/s12943-018-0838-5) contains supplementary material, which is available to authorized users.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
64.5
作者：
Nomura DK;Long JZ;Niessen S;Hoover HS;Ng SW;Cravatt BF
通讯作者：
Cravatt BF
影响因子：
29
作者：
Lamming DW;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
37.3
作者：
Jen J;Tang YA;Lu YH;Lin CC;Lai WW;Wang YC
通讯作者：
Wang YC
影响因子：
3.5
作者：
Cooper DR;Carter G;Li P;Patel R;Watson JE;Patel NA
通讯作者：
Patel NA