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Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis

BACKGROUND: Long non-coding RNAs (lncRNAs) are a class of non-protein coding RNAs greater than 200 nucleotides (nt) in length which have been shown to be significantly highly expressed in the heart tissue of mice undergoing thoracic aortic arch constriction (TAC). Micro RNAs (miRNAs) are a class of...

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Autores principales: Yang, Ya, Tang, Qianmei, Li, Yu, Dai, Lianjing, Li, Minfeng, Fu, Yongxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186230/
https://www.ncbi.nlm.nih.gov/pubmed/35693619
http://dx.doi.org/10.21037/jtd-22-501
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author Yang, Ya
Tang, Qianmei
Li, Yu
Dai, Lianjing
Li, Minfeng
Fu, Yongxin
author_facet Yang, Ya
Tang, Qianmei
Li, Yu
Dai, Lianjing
Li, Minfeng
Fu, Yongxin
author_sort Yang, Ya
collection PubMed
description BACKGROUND: Long non-coding RNAs (lncRNAs) are a class of non-protein coding RNAs greater than 200 nucleotides (nt) in length which have been shown to be significantly highly expressed in the heart tissue of mice undergoing thoracic aortic arch constriction (TAC). Micro RNAs (miRNAs) are a class of non-protein-coding RNAs. Many miRNAs have been reported to play a key role in the progression of myocardial hypertrophy. In this study, we aimed to investigate whether lncRNA reprogramming regulators (ROR) promotes hypoxic injury in cardiomyocytes by targeting and regulating the miR-145/HS1-associated protein X-1 (HAX-1) axis. METHODS: A mouse model of myocardial hypertrophy was established by conventional TAC method, and the cardiomyocytes were isolated. We transfected pcDNA3.0-ROR vector, pcDNA3.0-HAX-1 vector plasmid, and miR-145 simulant into cardiomyocytes with Lipofectamine 2000. Luciferase reporter gene was used to analyze the targeting relationship between genes. RESULTS: The expression of ROR in hypertrophic myocardium was significantly increased after phenylephrine (PE) intervention. After transfection with si-ROR, the ROR expression in hypertrophic cardiomyocytes treated with PE decreased significantly. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatine kinase (CK) decreased and superoxide dismutase (SOD) increased. The expression of miR-145 in cardiomyocytes was significantly down-regulated after PE treatment. In hypertrophic cardiomyocytes, after up-regulating the expression of miR-145, the relative messenger ribonucleic acid (mRNA) and protein expressions of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) induced by PE decreased. Compared with the miR-NC group, wild type (WT)-ROR activity in the miR-145 group was significantly inhibited (P<0.05), and mutant (MUT)-ROR activity had no significant change (P>0.05). When cardiomyocytes were transfected with HAX-1 3'URT WT vector along with miR-145 simulant, miR-145 inhibitor, and their respective controls. Compared with the control groups, the luciferase activity of cells transfected with simulant was significantly decreased (P<0.05), and increased in inhibitor group (P<0.05). Transfection of HAX-1 3'URT mutant vector did not show this phenomenon. ROR was negatively correlated with miR-145 expression and positively correlated with HAX-1 mRNA. CONCLUSIONS: The lncRNA ROR can promote the expression of HAX-1 by competitive binding with miR-145, so as to promote the pathophysiological process of myocardial hypertrophy.
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spelling pubmed-91862302022-06-11 Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis Yang, Ya Tang, Qianmei Li, Yu Dai, Lianjing Li, Minfeng Fu, Yongxin J Thorac Dis Original Article BACKGROUND: Long non-coding RNAs (lncRNAs) are a class of non-protein coding RNAs greater than 200 nucleotides (nt) in length which have been shown to be significantly highly expressed in the heart tissue of mice undergoing thoracic aortic arch constriction (TAC). Micro RNAs (miRNAs) are a class of non-protein-coding RNAs. Many miRNAs have been reported to play a key role in the progression of myocardial hypertrophy. In this study, we aimed to investigate whether lncRNA reprogramming regulators (ROR) promotes hypoxic injury in cardiomyocytes by targeting and regulating the miR-145/HS1-associated protein X-1 (HAX-1) axis. METHODS: A mouse model of myocardial hypertrophy was established by conventional TAC method, and the cardiomyocytes were isolated. We transfected pcDNA3.0-ROR vector, pcDNA3.0-HAX-1 vector plasmid, and miR-145 simulant into cardiomyocytes with Lipofectamine 2000. Luciferase reporter gene was used to analyze the targeting relationship between genes. RESULTS: The expression of ROR in hypertrophic myocardium was significantly increased after phenylephrine (PE) intervention. After transfection with si-ROR, the ROR expression in hypertrophic cardiomyocytes treated with PE decreased significantly. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatine kinase (CK) decreased and superoxide dismutase (SOD) increased. The expression of miR-145 in cardiomyocytes was significantly down-regulated after PE treatment. In hypertrophic cardiomyocytes, after up-regulating the expression of miR-145, the relative messenger ribonucleic acid (mRNA) and protein expressions of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) induced by PE decreased. Compared with the miR-NC group, wild type (WT)-ROR activity in the miR-145 group was significantly inhibited (P<0.05), and mutant (MUT)-ROR activity had no significant change (P>0.05). When cardiomyocytes were transfected with HAX-1 3'URT WT vector along with miR-145 simulant, miR-145 inhibitor, and their respective controls. Compared with the control groups, the luciferase activity of cells transfected with simulant was significantly decreased (P<0.05), and increased in inhibitor group (P<0.05). Transfection of HAX-1 3'URT mutant vector did not show this phenomenon. ROR was negatively correlated with miR-145 expression and positively correlated with HAX-1 mRNA. CONCLUSIONS: The lncRNA ROR can promote the expression of HAX-1 by competitive binding with miR-145, so as to promote the pathophysiological process of myocardial hypertrophy. AME Publishing Company 2022-05 /pmc/articles/PMC9186230/ /pubmed/35693619 http://dx.doi.org/10.21037/jtd-22-501 Text en 2022 Journal of Thoracic Disease. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Yang, Ya
Tang, Qianmei
Li, Yu
Dai, Lianjing
Li, Minfeng
Fu, Yongxin
Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis
title Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis
title_full Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis
title_fullStr Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis
title_full_unstemmed Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis
title_short Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis
title_sort long chain noncoding rna-ror promotes hypoxic injury of cardiomyocytes by targeting the mir-145/hax-1 axis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186230/
https://www.ncbi.nlm.nih.gov/pubmed/35693619
http://dx.doi.org/10.21037/jtd-22-501
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