What is the clinical evidence from this study?

Study design: Other. Population: Hepatocellular carcinoma (n=154). Intervention: High ATGL and NEAT1 expression vs. Low expression / normal liver tissue. Primary outcome: Overall survival and tissue expression positivity.

May 15, 2018Molecular Cancer264 citationsOpen Access

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

XLXirui LiuYunnan Agricultural University YLYingjian LiangHarbin Medical University RSRuipeng SongState Key Laboratory of Digital Medical Engineering

Key Result

ATGL was positively expressed in 76.11% of hepatocellular carcinoma tissues compared to 12.20% in normal liver tissues, and high expression of both ATGL and NEAT1 predicted poor overall survival.

Structured PICO

Population

Patients with hepatocellular carcinoma whose archival tumor and adjacent non-tumorous liver tissues were analyzed for gene expression and survival outcomes.

Exposure

Modulation of NEAT1 and ATGL (e.g., NEAT1 knockdown)

Comparator

Healthy liver tissues, control cells/mice

Outcome

HCC cell proliferation and expression levels of ATGL, DAG, and FFAsurrogate

The lncRNA NEAT1 modulates abnormal lipolysis via ATGL to drive hepatocellular carcinoma proliferation, suggesting a potential therapeutic target.

Main Result

Absolute Event Rate: 76.11% vs 12.2%

Limitations

The specific mechanism by which NEAT1 mediates fatty acid oxidation via PPARα requires further investigation.
Clinical findings are based on a relatively small retrospective cohort of archival tissues.

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/PPARα signaling. CONCLUSION: Our results reveal that NEAT1-modulates abnormal lipolysis via ATGL to drive HCC proliferation.

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