A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction

Abstract This study identified microRNAs involved in myocardial infarction (MI) through a novel system-level approach using RNA sequencing data in an MI mouse model. This approach involved the extraction of DEGs and DEmiRs from RNA-seq data in sham and MI samples and the subsequent selection of two...

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Autores principales:	Jin Ock Kim, Jei Hyoung Park, Taeyong Kim, Seong Eui Hong, Ji Young Lee, Kyoung Jin Nho, Chunghee Cho, Yong Sook Kim, Wan Seok Kang, Youngkeun Ahn, Do Han Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	System-level Approach Neonatal Rat Ventricular Myocytes (NRVMs) Differentially Expressed Genes (DEGs) Gene Set Enrichment Analysis (GSEA) Fragments Per Kilobase Of Exon Per Million Fragments (FPKM) Medicine R Science Q
Acceso en línea:	https://doaj.org/article/87f602c9a40c4a7f8e59fe82557b8e0d
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spelling	oai:doaj.org-article:87f602c9a40c4a7f8e59fe82557b8e0d2021-12-02T15:08:56ZA novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction10.1038/s41598-018-33020-x2045-2322https://doaj.org/article/87f602c9a40c4a7f8e59fe82557b8e0d2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33020-xhttps://doaj.org/toc/2045-2322Abstract This study identified microRNAs involved in myocardial infarction (MI) through a novel system-level approach using RNA sequencing data in an MI mouse model. This approach involved the extraction of DEGs and DEmiRs from RNA-seq data in sham and MI samples and the subsequent selection of two miRNAs: miR-30-5p (family) and miR-142a-5p, which were downregulated and upregulated in MI, respectively. Gene Set Enrichment Analysis (GSEA) using the predicted targets of the two miRNAs suggested that apoptosis is an essential gene ontology (GO)-associated term. In vitro functional assays using neonatal rat ventricular myocytes (NRVMs) demonstrated that miR-30-5p is anti-apoptotic and miR-142a-5p is pro-apoptotic. Luciferase assays showed that the apoptotic genes, Picalm and Skil, and the anti-apoptotic genes, Ghr and Kitl, are direct targets of miR-30-5p and miR-142a-5p, respectively. siRNA studies verified the results of the luciferase assays for target validation. The results of the system-level high throughput approach identified a pair of functionally antagonistic miRNAs and their targets in MI. This study provides an in-depth analysis of the role of miRNAs in the pathogenesis of MI which could lead to the development of therapeutic tools. The system-level approach could be used to identify miRNAs involved in variety of other diseases.Jin Ock KimJei Hyoung ParkTaeyong KimSeong Eui HongJi Young LeeKyoung Jin NhoChunghee ChoYong Sook KimWan Seok KangYoungkeun AhnDo Han KimNature PortfolioarticleSystem-level ApproachNeonatal Rat Ventricular Myocytes (NRVMs)Differentially Expressed Genes (DEGs)Gene Set Enrichment Analysis (GSEA)Fragments Per Kilobase Of Exon Per Million Fragments (FPKM)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	System-level Approach Neonatal Rat Ventricular Myocytes (NRVMs) Differentially Expressed Genes (DEGs) Gene Set Enrichment Analysis (GSEA) Fragments Per Kilobase Of Exon Per Million Fragments (FPKM) Medicine R Science Q
spellingShingle	System-level Approach Neonatal Rat Ventricular Myocytes (NRVMs) Differentially Expressed Genes (DEGs) Gene Set Enrichment Analysis (GSEA) Fragments Per Kilobase Of Exon Per Million Fragments (FPKM) Medicine R Science Q Jin Ock Kim Jei Hyoung Park Taeyong Kim Seong Eui Hong Ji Young Lee Kyoung Jin Nho Chunghee Cho Yong Sook Kim Wan Seok Kang Youngkeun Ahn Do Han Kim A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction
description	Abstract This study identified microRNAs involved in myocardial infarction (MI) through a novel system-level approach using RNA sequencing data in an MI mouse model. This approach involved the extraction of DEGs and DEmiRs from RNA-seq data in sham and MI samples and the subsequent selection of two miRNAs: miR-30-5p (family) and miR-142a-5p, which were downregulated and upregulated in MI, respectively. Gene Set Enrichment Analysis (GSEA) using the predicted targets of the two miRNAs suggested that apoptosis is an essential gene ontology (GO)-associated term. In vitro functional assays using neonatal rat ventricular myocytes (NRVMs) demonstrated that miR-30-5p is anti-apoptotic and miR-142a-5p is pro-apoptotic. Luciferase assays showed that the apoptotic genes, Picalm and Skil, and the anti-apoptotic genes, Ghr and Kitl, are direct targets of miR-30-5p and miR-142a-5p, respectively. siRNA studies verified the results of the luciferase assays for target validation. The results of the system-level high throughput approach identified a pair of functionally antagonistic miRNAs and their targets in MI. This study provides an in-depth analysis of the role of miRNAs in the pathogenesis of MI which could lead to the development of therapeutic tools. The system-level approach could be used to identify miRNAs involved in variety of other diseases.
format	article
author	Jin Ock Kim Jei Hyoung Park Taeyong Kim Seong Eui Hong Ji Young Lee Kyoung Jin Nho Chunghee Cho Yong Sook Kim Wan Seok Kang Youngkeun Ahn Do Han Kim
author_facet	Jin Ock Kim Jei Hyoung Park Taeyong Kim Seong Eui Hong Ji Young Lee Kyoung Jin Nho Chunghee Cho Yong Sook Kim Wan Seok Kang Youngkeun Ahn Do Han Kim
author_sort	Jin Ock Kim
title	A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction
title_short	A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction
title_full	A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction
title_fullStr	A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction
title_full_unstemmed	A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction
title_sort	novel system-level approach using rna-sequencing data identifies mir-30-5p and mir-142a-5p as key regulators of apoptosis in myocardial infarction
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/87f602c9a40c4a7f8e59fe82557b8e0d
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A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction

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