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The lncRNA NEAT1/miR-29b/Atg9a axis regulates IGFBPrP1-induced autophagy and activation of mouse hepatic stellate cells.
Life Sci. 2019 Nov 15; 237:116902.LS

Abstract

AIMS

Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) promotes hepatic stellate cell (HSC) autophagy and activation. However, the underlying mechanism remains unknown. Noncoding RNAs (ncRNAs) including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), have received increasing attention. We aimed to investigate the roles of the lncRNA nuclear enriched abundant transcript 1 (NEAT1), miR-29b, and autophagy related protein 9a (Atg9a), and their relationships with each other during IGFBPrP1-induced HSC autophagy and activation.

MAIN METHODS

Levels of NEAT1, miR-29b, Atg9a, and autophagy were detected in adenovirus-mediated IGFBPrP1 (AdIGFBPrP1)-treated mouse liver tissue and immortalized mouse hepatic stellate cell line JS1 transfected with either AdIGFBPrP1 or siIGFBPrP1. In AdIGFBPrP1-treated JS1 cells, autophagy and activation were detected after altering NEAT1, miR-29b, or Atg9a levels. In AdIGFBPrP1-treated JS1 cells, relationships among NEAT1, miR-29b, and Atg9a were explored using dual-luciferase reporter assays, Western blot, qRT-PCR, and immunofluorescence.

KEY FINDINGS

IGFBPrP1 increased levels of NEAT1, Atg9a, and autophagy while decreasing the level of miR-29b in mouse liver tissues and mouse HSCs. Moreover, NEAT1 increased HSC autophagy and activation while miR-29b decreased both processes. Atg9a also participated in IGFBPrP1-induced HSC autophagy and activation. Importantly, NEAT1, miR-29b, and Atg9a formed a NEAT1/miR-29b/Atg9a regulatory axis for IGFBPrP1-induced HSC autophagy and activation.

SIGNIFICANCE

Our study unveiled the new NEAT1/miR-29b/Atg9a regulatory axis involved in IGFBPrP1-induced mouse HSC autophagy and activation. The study thus provides new insights in the pathogenesis and potential therapeutic strategies of liver fibrosis.

Authors+Show Affiliations

Department of Gastroenterology and Hepatology, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China; Experimental Center of Science and Research, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China; Experimental Center of Science and Research, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China; Experimental Center of Science and Research, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China; Experimental Center of Science and Research, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China; Experimental Center of Science and Research, The First Clinical Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China. Electronic address: lixinliu6@hotmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31610195

Citation

Kong, Yangyang, et al. "The lncRNA NEAT1/miR-29b/Atg9a Axis Regulates IGFBPrP1-induced Autophagy and Activation of Mouse Hepatic Stellate Cells." Life Sciences, vol. 237, 2019, p. 116902.
Kong Y, Huang T, Zhang H, et al. The lncRNA NEAT1/miR-29b/Atg9a axis regulates IGFBPrP1-induced autophagy and activation of mouse hepatic stellate cells. Life Sci. 2019;237:116902.
Kong, Y., Huang, T., Zhang, H., Zhang, Q., Ren, J., Guo, X., Fan, H., & Liu, L. (2019). The lncRNA NEAT1/miR-29b/Atg9a axis regulates IGFBPrP1-induced autophagy and activation of mouse hepatic stellate cells. Life Sciences, 237, 116902. https://doi.org/10.1016/j.lfs.2019.116902
Kong Y, et al. The lncRNA NEAT1/miR-29b/Atg9a Axis Regulates IGFBPrP1-induced Autophagy and Activation of Mouse Hepatic Stellate Cells. Life Sci. 2019 Nov 15;237:116902. PubMed PMID: 31610195.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The lncRNA NEAT1/miR-29b/Atg9a axis regulates IGFBPrP1-induced autophagy and activation of mouse hepatic stellate cells. AU - Kong,Yangyang, AU - Huang,Tingjuan, AU - Zhang,Haiyan, AU - Zhang,Qianqian, AU - Ren,Junjie, AU - Guo,Xiaohong, AU - Fan,Huiqin, AU - Liu,Lixin, Y1 - 2019/10/11/ PY - 2019/07/26/received PY - 2019/09/13/revised PY - 2019/09/20/accepted PY - 2019/10/15/pubmed PY - 2019/11/26/medline PY - 2019/10/15/entrez KW - Autophagy KW - Hepatic stellate cells KW - Insulin-like growth factor binding protein-related protein 1 KW - Liver fibrosis KW - LncRNA NEAT1/miR-29b/Atg9a axis SP - 116902 EP - 116902 JF - Life sciences JO - Life Sci. VL - 237 N2 - AIMS: Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) promotes hepatic stellate cell (HSC) autophagy and activation. However, the underlying mechanism remains unknown. Noncoding RNAs (ncRNAs) including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), have received increasing attention. We aimed to investigate the roles of the lncRNA nuclear enriched abundant transcript 1 (NEAT1), miR-29b, and autophagy related protein 9a (Atg9a), and their relationships with each other during IGFBPrP1-induced HSC autophagy and activation. MAIN METHODS: Levels of NEAT1, miR-29b, Atg9a, and autophagy were detected in adenovirus-mediated IGFBPrP1 (AdIGFBPrP1)-treated mouse liver tissue and immortalized mouse hepatic stellate cell line JS1 transfected with either AdIGFBPrP1 or siIGFBPrP1. In AdIGFBPrP1-treated JS1 cells, autophagy and activation were detected after altering NEAT1, miR-29b, or Atg9a levels. In AdIGFBPrP1-treated JS1 cells, relationships among NEAT1, miR-29b, and Atg9a were explored using dual-luciferase reporter assays, Western blot, qRT-PCR, and immunofluorescence. KEY FINDINGS: IGFBPrP1 increased levels of NEAT1, Atg9a, and autophagy while decreasing the level of miR-29b in mouse liver tissues and mouse HSCs. Moreover, NEAT1 increased HSC autophagy and activation while miR-29b decreased both processes. Atg9a also participated in IGFBPrP1-induced HSC autophagy and activation. Importantly, NEAT1, miR-29b, and Atg9a formed a NEAT1/miR-29b/Atg9a regulatory axis for IGFBPrP1-induced HSC autophagy and activation. SIGNIFICANCE: Our study unveiled the new NEAT1/miR-29b/Atg9a regulatory axis involved in IGFBPrP1-induced mouse HSC autophagy and activation. The study thus provides new insights in the pathogenesis and potential therapeutic strategies of liver fibrosis. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/31610195/The_lncRNA_NEAT1/miR_29b/Atg9a_axis_regulates_IGFBPrP1_induced_autophagy_and_activation_of_mouse_hepatic_stellate_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(19)30829-X DB - PRIME DP - Unbound Medicine ER -