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Expression profiling analysis reveals key microRNA–mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles

BACKGROUND: Patients with transposition of the great arteries (TGA) have different connected systemic chambers and this determines the long-term morbidities and survival. Limited findings have been reported to systematically identify miRNA and mRNA expression levels in such cohorts of patients. In t...

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Autores principales: Abu-Halima, Masood, Wagner, Viktoria, Rishik, Shusruto, Raedle-Hurst, Tanja, Meese, Eckart, Abdul-Khaliq, Hashim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9878113/
https://www.ncbi.nlm.nih.gov/pubmed/36712263
http://dx.doi.org/10.3389/fcvm.2022.1056427
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author Abu-Halima, Masood
Wagner, Viktoria
Rishik, Shusruto
Raedle-Hurst, Tanja
Meese, Eckart
Abdul-Khaliq, Hashim
author_facet Abu-Halima, Masood
Wagner, Viktoria
Rishik, Shusruto
Raedle-Hurst, Tanja
Meese, Eckart
Abdul-Khaliq, Hashim
author_sort Abu-Halima, Masood
collection PubMed
description BACKGROUND: Patients with transposition of the great arteries (TGA) have different connected systemic chambers and this determines the long-term morbidities and survival. Limited findings have been reported to systematically identify miRNA and mRNA expression levels in such cohorts of patients. In this study, we aimed to characterize miRNAs, mRNAs, and miRNA–mRNA interaction networks in patients with TGA, with a systemic left (LV) and right ventricle (RV). MATERIALS AND METHODS: Large panel of human miRNA and mRNA microarrays were conducted to determine the genome-wide expression profiles in the blood of 16 TGA-RV patients, 16 TGA-LV patients, and 16 age and gender-matched controls. Using real-time quantitative PCR (RT-qPCR), the differential expression level of a single miRNA was validated. Enrichment analyses of altered miRNA and mRNA expression levels were identified using bioinformatics tools. RESULTS: Altered miRNA and mRNA expression levels were observed between TGA-RV and TGA-LV patients, together or separated, compared to controls. Among the deregulated miRNAs and mRNAs, 39 and 101 miRNAs were identified as significantly differentially expressed in patients with TGA (both TGA-RV and TGA-LV) and TGA-RV, when compared to matched controls. Furthermore, 51 miRNAs were identified as significantly differentially expressed in patients with TGA-RV when compared to patients with TGA-LV. RT-qPCR relative expression level was highly consistent with microarray analysis results. Similarly, 36 and 164 mRNAs were identified as significantly differentially expressed in patients with TGA (both TGA-RV and TGA-LV) and TGA-RV, when compared to matched controls. Additionally, miR-140-3p showed a higher expression level in patients with overt heart failure (FC = 1.54; P = 0.001) and miR-502-3p showed a higher expression level in patients died due to cardiac death (FC = 1.41; P = 0.011). Integrative analysis resulted in 21 and 23 target genes with higher and lower expression levels, respectively (r ≥ 0.50 and P < 0.05). These target genes (i.e., 21 and 23 target genes) showed an inverse direction of regulation with miRNA and exhibited a miRNA binding site position within the 3′UTR of the target gene. CONCLUSION: Our findings provide new insights into a potential molecular biomarker(s) for patients with TGA that may guide better risk stratification and the development of novel targeting therapies. Future studies are needed to investigate the potential significance of miRNAs and mRNAs in TGA-related cardiovascular diseases.
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spelling pubmed-98781132023-01-27 Expression profiling analysis reveals key microRNA–mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles Abu-Halima, Masood Wagner, Viktoria Rishik, Shusruto Raedle-Hurst, Tanja Meese, Eckart Abdul-Khaliq, Hashim Front Cardiovasc Med Cardiovascular Medicine BACKGROUND: Patients with transposition of the great arteries (TGA) have different connected systemic chambers and this determines the long-term morbidities and survival. Limited findings have been reported to systematically identify miRNA and mRNA expression levels in such cohorts of patients. In this study, we aimed to characterize miRNAs, mRNAs, and miRNA–mRNA interaction networks in patients with TGA, with a systemic left (LV) and right ventricle (RV). MATERIALS AND METHODS: Large panel of human miRNA and mRNA microarrays were conducted to determine the genome-wide expression profiles in the blood of 16 TGA-RV patients, 16 TGA-LV patients, and 16 age and gender-matched controls. Using real-time quantitative PCR (RT-qPCR), the differential expression level of a single miRNA was validated. Enrichment analyses of altered miRNA and mRNA expression levels were identified using bioinformatics tools. RESULTS: Altered miRNA and mRNA expression levels were observed between TGA-RV and TGA-LV patients, together or separated, compared to controls. Among the deregulated miRNAs and mRNAs, 39 and 101 miRNAs were identified as significantly differentially expressed in patients with TGA (both TGA-RV and TGA-LV) and TGA-RV, when compared to matched controls. Furthermore, 51 miRNAs were identified as significantly differentially expressed in patients with TGA-RV when compared to patients with TGA-LV. RT-qPCR relative expression level was highly consistent with microarray analysis results. Similarly, 36 and 164 mRNAs were identified as significantly differentially expressed in patients with TGA (both TGA-RV and TGA-LV) and TGA-RV, when compared to matched controls. Additionally, miR-140-3p showed a higher expression level in patients with overt heart failure (FC = 1.54; P = 0.001) and miR-502-3p showed a higher expression level in patients died due to cardiac death (FC = 1.41; P = 0.011). Integrative analysis resulted in 21 and 23 target genes with higher and lower expression levels, respectively (r ≥ 0.50 and P < 0.05). These target genes (i.e., 21 and 23 target genes) showed an inverse direction of regulation with miRNA and exhibited a miRNA binding site position within the 3′UTR of the target gene. CONCLUSION: Our findings provide new insights into a potential molecular biomarker(s) for patients with TGA that may guide better risk stratification and the development of novel targeting therapies. Future studies are needed to investigate the potential significance of miRNAs and mRNAs in TGA-related cardiovascular diseases. Frontiers Media S.A. 2023-01-12 /pmc/articles/PMC9878113/ /pubmed/36712263 http://dx.doi.org/10.3389/fcvm.2022.1056427 Text en Copyright © 2023 Abu-Halima, Wagner, Rishik, Raedle-Hurst, Meese and Abdul-Khaliq. 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 Cardiovascular Medicine
Abu-Halima, Masood
Wagner, Viktoria
Rishik, Shusruto
Raedle-Hurst, Tanja
Meese, Eckart
Abdul-Khaliq, Hashim
Expression profiling analysis reveals key microRNA–mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles
title Expression profiling analysis reveals key microRNA–mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles
title_full Expression profiling analysis reveals key microRNA–mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles
title_fullStr Expression profiling analysis reveals key microRNA–mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles
title_full_unstemmed Expression profiling analysis reveals key microRNA–mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles
title_short Expression profiling analysis reveals key microRNA–mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles
title_sort expression profiling analysis reveals key microrna–mrna interactions in patients with transposition of the great arteries and systemic left and right ventricles
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9878113/
https://www.ncbi.nlm.nih.gov/pubmed/36712263
http://dx.doi.org/10.3389/fcvm.2022.1056427
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