期刊
CELL DEATH DISCOVERY
卷 7, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41420-021-00632-8
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资金
- National Natural Science Foundation of China [81971495, 91442117]
- CAMS Innovation Fund for Medical Sciences
- National Science Foundation of Jiangsu Province [BRA2017533, BK20191490]
- State Key Laboratory of Reproductive Medicine [SKLRM-K202001]
- Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials
The study highlighted the regulatory role of lncRNA NEAT1 and miR-139-5p in liver fibrosis progression, with NEAT1 promoting HSCs activation by sponging miR-139-5p. The overexpression of miR-139-5p or knockdown of NEAT1 alleviated liver fibrosis in vivo by targeting the beta-catenin/SOX9/TGF-beta 1 pathway.
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 beta-catenin. The overexpression of beta-catenin promoted HSCs activation. Moreover, we found that beta-catenin could interact with SOX9 promoted HSCs activation. Our further studies demonstrated that SOX9 could bind with the TGF-beta 1 promoter and promoted the transcription activity of TGF-beta 1. The upregulation of TGF-beta 1 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 beta-catenin/SOX9/TGF-beta 1 Pathway.
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