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


Journal

Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035

Informations de publication

Date de publication:
16 Sep 2021
Historique:
received: 31 03 2021
accepted: 27 08 2021
revised: 23 08 2021
entrez: 17 9 2021
pubmed: 18 9 2021
medline: 18 9 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34531378
doi: 10.1038/s41420-021-00632-8
pii: 10.1038/s41420-021-00632-8
pmc: PMC8446030
doi:

Types de publication

Journal Article

Langues

eng

Pagination

243

Subventions

Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81971495

Informations de copyright

© 2021. The Author(s).

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Auteurs

Qi Wang (Q)

School of Medicine, Southeast University, Nanjing, China.
Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.

Song Wei (S)

School of Medicine, Southeast University, Nanjing, China.
Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.

Lei Li (L)

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.

Qingfa Bu (Q)

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.

Haoming Zhou (H)

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.

Wantong Su (W)

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.

Zheng Liu (Z)

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.

Mingming Wang (M)

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.

Ling Lu (L)

School of Medicine, Southeast University, Nanjing, China. lvling@njmu.edu.cn.
Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China. lvling@njmu.edu.cn.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China. lvling@njmu.edu.cn.
State Key Laboratory of Reproductive Medicine, Nanjing, China. lvling@njmu.edu.cn.

Classifications MeSH