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lncRNA Mirt1: A Critical Regulatory Factor in Chronic Intermittent Hypoxia Exaggerated Post-MI Cardiac Remodeling
Chronic intermittent hypoxia (CIH) is the main feature of obstructive sleep apnea (OSA) and is known to exaggerate cardiac remodeling after myocardial infarction (MI). However, the specific contribution of CIH to overall OSA-induced pathological complications and the transcriptomic mechanisms underl...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864109/ https://www.ncbi.nlm.nih.gov/pubmed/35222538 http://dx.doi.org/10.3389/fgene.2022.818823 |
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author | Wang, Xinxia Li, Zexuan Du, Yunhui Xing, Yuanyuan Guo, Yingying Zhang, Yushi Guo, Ruifeng Gong, Wei Nie, Shaoping Wang, Xiao |
author_facet | Wang, Xinxia Li, Zexuan Du, Yunhui Xing, Yuanyuan Guo, Yingying Zhang, Yushi Guo, Ruifeng Gong, Wei Nie, Shaoping Wang, Xiao |
author_sort | Wang, Xinxia |
collection | PubMed |
description | Chronic intermittent hypoxia (CIH) is the main feature of obstructive sleep apnea (OSA) and is known to exaggerate cardiac remodeling after myocardial infarction (MI). However, the specific contribution of CIH to overall OSA-induced pathological complications and the transcriptomic mechanisms underlying CIH-exaggerated post-MI remodeling remains unclear. In this study, we used RNA-sequencing to construct the expression profiles of cardiac mRNAs, microRNAs, and long non-coding RNAs (lncRNA) in four groups of C57BL/6J mice (Sham, CIH, MI, MI + CIH) to evaluate how CIH regulates cardiac remodeling after MI. Compared with the other three groups, the MI + CIH group exhibited 345 lncRNAs, 35 microRNAs, and 5,220 differentially expressed mRNAs. Further analysis showed that CIH led to significant changes in Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the differentially expressed mRNAs. Co-expression network analysis identified two core lncRNAs (Mirt1 and AC125351.1) and two core microRNAs (miR-466i-5p and miR-574-5p) during the development of CIH-exaggerated post-MI remodeling, and they were verified by quantitative real-time PCR (qRT-PCR). LncRNA-mRNA correlation analysis further showed that lncRNA Mirt1 was positively correlated with Apbb1ip and Lcp2. In addition, microRNA-mRNA correlation analysis showed that microRNA miR-466i-5p was positively correlated with Snai2, Cdc27, and Ngfr. Furthermore, combining with lncRNA-mRNA and miRNA-mRNA networks, 44 RNAs were identified in the competitive endogenous RNA (ceRNA) network. Mirt1 acts as a ceRNA to bind to miR-466i-5p to further regulate the expression levels of the target gene, thereby aggravating cardiac remodeling after MI. In conclusion, our study provides a systematic perspective on the potential functions of mRNAs, microRNAs, and lncRNAs in CIH-exaggerated post-MI cardiac remodeling. Our data suggest that lncRNA Mirt1 may be the most critical regulator of MI aggravated by CIH. |
format | Online Article Text |
id | pubmed-8864109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88641092022-02-24 lncRNA Mirt1: A Critical Regulatory Factor in Chronic Intermittent Hypoxia Exaggerated Post-MI Cardiac Remodeling Wang, Xinxia Li, Zexuan Du, Yunhui Xing, Yuanyuan Guo, Yingying Zhang, Yushi Guo, Ruifeng Gong, Wei Nie, Shaoping Wang, Xiao Front Genet Genetics Chronic intermittent hypoxia (CIH) is the main feature of obstructive sleep apnea (OSA) and is known to exaggerate cardiac remodeling after myocardial infarction (MI). However, the specific contribution of CIH to overall OSA-induced pathological complications and the transcriptomic mechanisms underlying CIH-exaggerated post-MI remodeling remains unclear. In this study, we used RNA-sequencing to construct the expression profiles of cardiac mRNAs, microRNAs, and long non-coding RNAs (lncRNA) in four groups of C57BL/6J mice (Sham, CIH, MI, MI + CIH) to evaluate how CIH regulates cardiac remodeling after MI. Compared with the other three groups, the MI + CIH group exhibited 345 lncRNAs, 35 microRNAs, and 5,220 differentially expressed mRNAs. Further analysis showed that CIH led to significant changes in Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the differentially expressed mRNAs. Co-expression network analysis identified two core lncRNAs (Mirt1 and AC125351.1) and two core microRNAs (miR-466i-5p and miR-574-5p) during the development of CIH-exaggerated post-MI remodeling, and they were verified by quantitative real-time PCR (qRT-PCR). LncRNA-mRNA correlation analysis further showed that lncRNA Mirt1 was positively correlated with Apbb1ip and Lcp2. In addition, microRNA-mRNA correlation analysis showed that microRNA miR-466i-5p was positively correlated with Snai2, Cdc27, and Ngfr. Furthermore, combining with lncRNA-mRNA and miRNA-mRNA networks, 44 RNAs were identified in the competitive endogenous RNA (ceRNA) network. Mirt1 acts as a ceRNA to bind to miR-466i-5p to further regulate the expression levels of the target gene, thereby aggravating cardiac remodeling after MI. In conclusion, our study provides a systematic perspective on the potential functions of mRNAs, microRNAs, and lncRNAs in CIH-exaggerated post-MI cardiac remodeling. Our data suggest that lncRNA Mirt1 may be the most critical regulator of MI aggravated by CIH. Frontiers Media S.A. 2022-02-09 /pmc/articles/PMC8864109/ /pubmed/35222538 http://dx.doi.org/10.3389/fgene.2022.818823 Text en Copyright © 2022 Wang, Li, Du, Xing, Guo, Zhang, Guo, Gong, Nie and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Wang, Xinxia Li, Zexuan Du, Yunhui Xing, Yuanyuan Guo, Yingying Zhang, Yushi Guo, Ruifeng Gong, Wei Nie, Shaoping Wang, Xiao lncRNA Mirt1: A Critical Regulatory Factor in Chronic Intermittent Hypoxia Exaggerated Post-MI Cardiac Remodeling |
title | lncRNA Mirt1: A Critical Regulatory Factor in Chronic Intermittent Hypoxia Exaggerated Post-MI Cardiac Remodeling |
title_full | lncRNA Mirt1: A Critical Regulatory Factor in Chronic Intermittent Hypoxia Exaggerated Post-MI Cardiac Remodeling |
title_fullStr | lncRNA Mirt1: A Critical Regulatory Factor in Chronic Intermittent Hypoxia Exaggerated Post-MI Cardiac Remodeling |
title_full_unstemmed | lncRNA Mirt1: A Critical Regulatory Factor in Chronic Intermittent Hypoxia Exaggerated Post-MI Cardiac Remodeling |
title_short | lncRNA Mirt1: A Critical Regulatory Factor in Chronic Intermittent Hypoxia Exaggerated Post-MI Cardiac Remodeling |
title_sort | lncrna mirt1: a critical regulatory factor in chronic intermittent hypoxia exaggerated post-mi cardiac remodeling |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864109/ https://www.ncbi.nlm.nih.gov/pubmed/35222538 http://dx.doi.org/10.3389/fgene.2022.818823 |
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