miR-139-5p sponged by LncRNA NEAT1 regulates liver fibrosis via targeting β-catenin/SOX9/TGF-β1 pathway.

Abstract

Liver fibrosis is a patho-physiological process which can develop into cirrhosis, and hepatic carcinoma without intervention. Our study extensively investigated the mechanisms of lncRNA NEAT1 and miR-139-5p in regulating liver fibrosis progression. Our results demonstrated that the expression of lncRNA NEAT1 was increased and the expression of miR-139-5p was decreased in fibrotic liver tissues. LncRNA NEAT1 could sponge miR-139-5p and promoted hepatic stellate cells (HSCs) activation by directly inhibiting the expression of miR-139-5p. The co-localization of lncRNA NEAT1 with miR-139-5p was shown in the cytosols of activated HSCs. miR-139-5p upregulation could suppress the expression of β-catenin. The overexpression of β-catenin promoted HSCs activation. Moreover, we found that β-catenin could interact with SOX9 promoted HSCs activation. Our further studies demonstrated that SOX9 could bind with the TGF-β1 promoter and promoted the transcription activity of TGF-β1. The upregulation of TGF-β1 further promoted HSCs activation. In vivo study also suggested that lncRNA NEAT1 knockdown and miR-139-5p overexpression alleviated murine liver fibrosis. LncRNA NEAT1 exacerbated liver fibrosis by suppressing the expression of miR-139-5p. Collectively, our study suggested that miR-139-5p sponged by lncRNA NEAT1 regulated liver fibrosis via targeting β-catenin/SOX9/TGF-β1 Pathway.

• Authors: Qi Wang, Song Wei, Lei Li, Qingfa Bu, Haoming Zhou, Wantong Su, Zheng Liu, Mingming Wang, Ling Lu
• Journal: Cell death discovery (Cell Death Discov) Vol. 7 Issue 1 Pg. 243 (Sep 16 2021) ISSN: 2058-7716 [Print] United States
• PMID: 34531378 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).