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lncRNA NEAT1 regulates fibrosis and inflammatory response induced by nonalcoholic fatty liver by regulating miR-506/GLI3

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European Cytokine Network Aims and scope

Abstract

Background: As one of the most common liver disorders worldwide, nonalcoholic fatty liver disease (NAFLD) begins with the abnormal accumulation of triglyceride (TG) in the liver and can lead to inflammation and fibrosis. Long noncoding RNA (lncRNA) NEAT1 was reported to promote NAFLD progress. However, its molecular mechanism in NAFLD was not fully clear. Method: In vitro cellular model of NAFLD was established with BRL3A cell treated by free fatty acid (FFA). Cell Counting Kit-8 (CCK-8) assay was carried out to assess cell proliferation. The expression of mRNA and protein of inflammation and fibrosis in BRL3A cell was detected by qRT-PCR and Western blot. Bioinformatics and dual-luciferase reporter assays were used to predict and validate the interaction between NEAT1 and miR-506 as well as GLI3 and miR-506. Results: NEAT1 was upregulated while miR-506 was downregulated in the progression of NAFLD. Meanwhile, NEAT1 and miR-506 were proved to regulate fibrosis, inflammatory response, and lipid metabolism. Knockdown of NEAT1 inhibited GLI3 expression and promoted miR- 506 expression, Overexpression of miR-506 inhibited NEAT1 and GLI3 expression. Moreover, dual-luciferase reporter assays proved that miR-506 could bind to NEAT1 and GLI3, whereas NEAT1 could sponge miR-506 to regulate GLI3 expression. Conclusion: lncRNA NEAT1 could regulate fibrosis, inflammatory response, and lipid metabolism via the miR-506/GLI3 axis as a ceRNA, which is a novel mechanistic role in the regulation of NAFLD. These results provide a new potential treatment target for NAFLD.

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Abbreviations

NAFLD:

non-alcoholic fatty liver disease

HCC:

hepatocellular carcinoma

NEAT1:

nuclear enriched abundant transcript 1

lncRNAs:

long non-coding RNAs

qRT-PCR:

quantitative realtime polymerase chain reaction

FFA:

free fatty acid

DMEM:

dulbecco’s modified eagle medium

ACC:

acetyl-CoA carboxylase

CCK-8:

Cell Counting Kit-8

Hh:

hedgehog

ceRNA:

competing endogenous RNA

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Acknowledgments

We would like to give our sincere gratitude to the reviewers for their constructive comments.

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Authors and Affiliations

  1. Department of Pharmacy, Wenzhou People’s Hospital, 325000, Wenzhou, Zhejiang Province, P.R. China

    Qiong Wang

  2. Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, New Campus of Nanbaixiang Wenyi First Hospital, Ouhai District, Wenzhou, Zhejiang Province, 325000, P.R. China

    Si-Si Jin, Xian-Fan Lin, Ju-Zeng Zheng & Hua-Qin Guan

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  1. Si-Si Jin
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  2. Xian-Fan Lin
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  3. Ju-Zeng Zheng
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Correspondence to Hua-Qin Guan.

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The authors declare that there are no conflicts of interest.

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Jin, SS., Lin, XF., Zheng, JZ. et al. lncRNA NEAT1 regulates fibrosis and inflammatory response induced by nonalcoholic fatty liver by regulating miR-506/GLI3. Eur Cytokine Netw 30, 98–106 (2019). https://doi.org/10.1684/ecn.2019.0432

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