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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...

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Autores principales: Zou, Lei, Shi, Cuifen, Wang, Dawei, Cheng, Juan, Wang, Qi, Wang, Lei, Yang, Guoya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
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.
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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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