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

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. M...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953401/
https://www.ncbi.nlm.nih.gov/pubmed/29764424
http://dx.doi.org/10.1186/s12943-018-0838-5
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author 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
author_facet 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
author_sort Liu, Xirui
collection PubMed
description 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/PPARα signaling. CONCLUSION: Our results reveal that NEAT1-modulates abnormal lipolysis via ATGL to drive HCC proliferation. ELECTRONIC SUPPLEMENTARY MATERIAL: 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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spelling pubmed-59534012018-05-21 Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation 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 Mol Cancer Research 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/PPARα signaling. CONCLUSION: Our results reveal that NEAT1-modulates abnormal lipolysis via ATGL to drive HCC proliferation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12943-018-0838-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-15 /pmc/articles/PMC5953401/ /pubmed/29764424 http://dx.doi.org/10.1186/s12943-018-0838-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
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
Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation
title Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation
title_full Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation
title_fullStr Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation
title_full_unstemmed Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation
title_short Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation
title_sort long non-coding rna neat1-modulated abnormal lipolysis via atgl drives hepatocellular carcinoma proliferation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953401/
https://www.ncbi.nlm.nih.gov/pubmed/29764424
http://dx.doi.org/10.1186/s12943-018-0838-5
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