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Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis
Ischemic cardiomyopathy (ICM), characterized by pre-existing myocardial infarction or severe coronary artery disease, is the major cause of heart failure (HF). Identification of novel transcriptional regulators in ischemic HF can provide important biomarkers for developing new diagnostic and therape...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278960/ https://www.ncbi.nlm.nih.gov/pubmed/32423033 http://dx.doi.org/10.3390/ijms21103472 |
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author | Alimadadi, Ahmad Aryal, Sachin Manandhar, Ishan Joe, Bina Cheng, Xi |
author_facet | Alimadadi, Ahmad Aryal, Sachin Manandhar, Ishan Joe, Bina Cheng, Xi |
author_sort | Alimadadi, Ahmad |
collection | PubMed |
description | Ischemic cardiomyopathy (ICM), characterized by pre-existing myocardial infarction or severe coronary artery disease, is the major cause of heart failure (HF). Identification of novel transcriptional regulators in ischemic HF can provide important biomarkers for developing new diagnostic and therapeutic strategies. In this study, we used four RNA-seq datasets from four different studies, including 41 ICM and 42 non-failing control (NF) samples of human left ventricle tissues, to perform the first RNA-seq meta-analysis in the field of clinical ICM, in order to identify important transcriptional regulators and their targeted genes involved in ICM. Our meta-analysis identified 911 differentially expressed genes (DEGs) with 582 downregulated and 329 upregulated. Interestingly, 54 new DEGs were detected only by meta-analysis but not in individual datasets. Upstream regulator analysis through Ingenuity Pathway Analysis (IPA) identified three key transcriptional regulators. TBX5 was identified as the only inhibited regulator (z-score = −2.89). F2R and SFRP4 were identified as the activated regulators (z-scores = 2.56 and 2.00, respectively). Multiple downstream genes regulated by TBX5, F2R, and SFRP4 were involved in ICM-related diseases such as HF and arrhythmia. Overall, our study is the first to perform an RNA-seq meta-analysis for clinical ICM and provides robust candidate genes, including three key transcriptional regulators, for future diagnostic and therapeutic applications in ischemic heart failure. |
format | Online Article Text |
id | pubmed-7278960 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72789602020-06-15 Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis Alimadadi, Ahmad Aryal, Sachin Manandhar, Ishan Joe, Bina Cheng, Xi Int J Mol Sci Article Ischemic cardiomyopathy (ICM), characterized by pre-existing myocardial infarction or severe coronary artery disease, is the major cause of heart failure (HF). Identification of novel transcriptional regulators in ischemic HF can provide important biomarkers for developing new diagnostic and therapeutic strategies. In this study, we used four RNA-seq datasets from four different studies, including 41 ICM and 42 non-failing control (NF) samples of human left ventricle tissues, to perform the first RNA-seq meta-analysis in the field of clinical ICM, in order to identify important transcriptional regulators and their targeted genes involved in ICM. Our meta-analysis identified 911 differentially expressed genes (DEGs) with 582 downregulated and 329 upregulated. Interestingly, 54 new DEGs were detected only by meta-analysis but not in individual datasets. Upstream regulator analysis through Ingenuity Pathway Analysis (IPA) identified three key transcriptional regulators. TBX5 was identified as the only inhibited regulator (z-score = −2.89). F2R and SFRP4 were identified as the activated regulators (z-scores = 2.56 and 2.00, respectively). Multiple downstream genes regulated by TBX5, F2R, and SFRP4 were involved in ICM-related diseases such as HF and arrhythmia. Overall, our study is the first to perform an RNA-seq meta-analysis for clinical ICM and provides robust candidate genes, including three key transcriptional regulators, for future diagnostic and therapeutic applications in ischemic heart failure. MDPI 2020-05-14 /pmc/articles/PMC7278960/ /pubmed/32423033 http://dx.doi.org/10.3390/ijms21103472 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Alimadadi, Ahmad Aryal, Sachin Manandhar, Ishan Joe, Bina Cheng, Xi Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis |
title | Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis |
title_full | Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis |
title_fullStr | Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis |
title_full_unstemmed | Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis |
title_short | Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis |
title_sort | identification of upstream transcriptional regulators of ischemic cardiomyopathy using cardiac rna-seq meta-analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278960/ https://www.ncbi.nlm.nih.gov/pubmed/32423033 http://dx.doi.org/10.3390/ijms21103472 |
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