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Long non-coding RNA-non-coding RNA activated by DNA damage inhibition suppresses hepatic stellate cell activation via microRNA-495-3p/sphingosine 1-phosphate receptor 3 axis
Hepatic fibrosis is a damage repair response caused by multiple factors. A growing body of research suggests that long non-coding RNAs (lncRNAs) are involved in a wide range of biological processes, and thus regulate disease progression, including hepatic fibrosis. In this study, we investigated the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973981/ https://www.ncbi.nlm.nih.gov/pubmed/35200103 http://dx.doi.org/10.1080/21655979.2022.2037841 |
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author | Zou, Lei Shi, Cuifen Wang, Dawei Cheng, Juan Wang, Qi Wang, Lei Yang, Guoya |
author_facet | Zou, Lei Shi, Cuifen Wang, Dawei Cheng, Juan Wang, Qi Wang, Lei Yang, Guoya |
author_sort | Zou, Lei |
collection | PubMed |
description | Hepatic fibrosis is a damage repair response caused by multiple factors. A growing body of research suggests that long non-coding RNAs (lncRNAs) are involved in a wide range of biological processes, and thus regulate disease progression, including hepatic fibrosis. In this study, we investigated the mechanisms of the long non-coding RNA-non-coding RNA activated by DNA damage (NORAD) in modulating hepatic fibrosis development. Platelet-derived growth factor-BB (PDGF-BB) was used to activate LX-2 hepatic stellate cells (HSCs). The expression of NORAD and microRNA (miR)-495-3p was determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The effects of PDGF-BB on LX-2 cell viability, migration, invasion, and apoptosis were evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), Transwell, flow cytometry, and Western blot assays. The activation of HSCs was further verified by examining the expression of the typical markers, alpha smooth muscle actin (α-SMA) and collagen I (Col1α1), using qRT-PCR and Western blot assays. StarBase and dual-luciferase reporter assays were used to assess the binding relationship between miR-495-3p and NORAD. The NORAD levels remarkably increased, whereas the miR-495-3p levels decreased, in PDGF-BB-treated LX-2 cells. miR-495-3p was a putative downstream target of NORAD. NORAD silencing played an anti-fibrotic role by targeting miR-495-3p; this was accomplished by hindering PDGF-BB-treated LX-2 cell viability, migration, and invasion, decreasing the levels of α-SMA and Col1α1, and promoting apoptosis. miR-495-3p protected against hepatic fibrosis by inhibiting sphingosine 1-phosphate receptor 3 (S1PR3) expression. In summary, NORAD silencing inhibited hepatic fibrosis by suppressing HSC activation via the miR-495-3p/S1PR3 axis. |
format | Online Article Text |
id | pubmed-8973981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-89739812022-04-02 Long non-coding RNA-non-coding RNA activated by DNA damage inhibition suppresses hepatic stellate cell activation via microRNA-495-3p/sphingosine 1-phosphate receptor 3 axis Zou, Lei Shi, Cuifen Wang, Dawei Cheng, Juan Wang, Qi Wang, Lei Yang, Guoya Bioengineered Research Paper Hepatic fibrosis is a damage repair response caused by multiple factors. A growing body of research suggests that long non-coding RNAs (lncRNAs) are involved in a wide range of biological processes, and thus regulate disease progression, including hepatic fibrosis. In this study, we investigated the mechanisms of the long non-coding RNA-non-coding RNA activated by DNA damage (NORAD) in modulating hepatic fibrosis development. Platelet-derived growth factor-BB (PDGF-BB) was used to activate LX-2 hepatic stellate cells (HSCs). The expression of NORAD and microRNA (miR)-495-3p was determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The effects of PDGF-BB on LX-2 cell viability, migration, invasion, and apoptosis were evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), Transwell, flow cytometry, and Western blot assays. The activation of HSCs was further verified by examining the expression of the typical markers, alpha smooth muscle actin (α-SMA) and collagen I (Col1α1), using qRT-PCR and Western blot assays. StarBase and dual-luciferase reporter assays were used to assess the binding relationship between miR-495-3p and NORAD. The NORAD levels remarkably increased, whereas the miR-495-3p levels decreased, in PDGF-BB-treated LX-2 cells. miR-495-3p was a putative downstream target of NORAD. NORAD silencing played an anti-fibrotic role by targeting miR-495-3p; this was accomplished by hindering PDGF-BB-treated LX-2 cell viability, migration, and invasion, decreasing the levels of α-SMA and Col1α1, and promoting apoptosis. miR-495-3p protected against hepatic fibrosis by inhibiting sphingosine 1-phosphate receptor 3 (S1PR3) expression. In summary, NORAD silencing inhibited hepatic fibrosis by suppressing HSC activation via the miR-495-3p/S1PR3 axis. Taylor & Francis 2022-02-24 /pmc/articles/PMC8973981/ /pubmed/35200103 http://dx.doi.org/10.1080/21655979.2022.2037841 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Zou, Lei Shi, Cuifen Wang, Dawei Cheng, Juan Wang, Qi Wang, Lei Yang, Guoya Long non-coding RNA-non-coding RNA activated by DNA damage inhibition suppresses hepatic stellate cell activation via microRNA-495-3p/sphingosine 1-phosphate receptor 3 axis |
title | Long non-coding RNA-non-coding RNA activated by DNA damage inhibition suppresses hepatic stellate cell activation via microRNA-495-3p/sphingosine 1-phosphate receptor 3 axis |
title_full | Long non-coding RNA-non-coding RNA activated by DNA damage inhibition suppresses hepatic stellate cell activation via microRNA-495-3p/sphingosine 1-phosphate receptor 3 axis |
title_fullStr | Long non-coding RNA-non-coding RNA activated by DNA damage inhibition suppresses hepatic stellate cell activation via microRNA-495-3p/sphingosine 1-phosphate receptor 3 axis |
title_full_unstemmed | Long non-coding RNA-non-coding RNA activated by DNA damage inhibition suppresses hepatic stellate cell activation via microRNA-495-3p/sphingosine 1-phosphate receptor 3 axis |
title_short | Long non-coding RNA-non-coding RNA activated by DNA damage inhibition suppresses hepatic stellate cell activation via microRNA-495-3p/sphingosine 1-phosphate receptor 3 axis |
title_sort | long non-coding rna-non-coding rna activated by dna damage inhibition suppresses hepatic stellate cell activation via microrna-495-3p/sphingosine 1-phosphate receptor 3 axis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973981/ https://www.ncbi.nlm.nih.gov/pubmed/35200103 http://dx.doi.org/10.1080/21655979.2022.2037841 |
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