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Identification of functional lncRNAs in atrial fibrillation based on RNA sequencing

BACKGROUND: Atrial fibrillation (AF) is one of the most common arrhythmia contributing to serious conditions such as stroke and heart failure. Recent studies demonstrated that long noncoding RNAs (lncRNAs) were related to cardiovascular disease. However, the molecular mechanisms of AF are not fully...

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Autores principales: You, Yangyang, Wang, Wei, Zhu, Wenshu, Xu, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626701/
https://www.ncbi.nlm.nih.gov/pubmed/37932671
http://dx.doi.org/10.1186/s12872-023-03573-5
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author You, Yangyang
Wang, Wei
Zhu, Wenshu
Xu, Jian
author_facet You, Yangyang
Wang, Wei
Zhu, Wenshu
Xu, Jian
author_sort You, Yangyang
collection PubMed
description BACKGROUND: Atrial fibrillation (AF) is one of the most common arrhythmia contributing to serious conditions such as stroke and heart failure. Recent studies demonstrated that long noncoding RNAs (lncRNAs) were related to cardiovascular disease. However, the molecular mechanisms of AF are not fully clear. This study intended to discover lncRNAs that are differentially expressed in AF compared with controls and evaluate the potential functions of these lncRNAs. METHODS: Ninety-seven patients (49 patients with AF and 48 patients without AF) were included in this study. Among these patients, leucocyte suspensions of 3 AF patients and 3 controls were sent for RNA-seq analysis to select differentially expressed lncRNA and mRNA. Different lncRNA expressions were validated in another samples (46 AF patients and 45 controls). Gene ontology (GO) enrichment analysis was conducted to annotate the function of selected mRNAs. Alternative splicing (AS) analysis was performed and a lncRNA-mRNA network was also constructed. The receiver operating characteristics (ROC) curve was used to evaluate diagnostic values. Logistic regression analysis was utilized to assess the risk or protective factor of AF. RESULTS: A total of 223 mRNAs and 105 lncRNAs were detected in AF patients compared with controls. Total 4 lncRNAs (LINC01781, AC009509.2, AL662844.3, AL662844.4) associated with AF were picked out for validation in another samples by quantitative real-time PCR (qRT-PCR), detecting that upregulated AC009509.2 and downregulated LINC01781 in AF patients. Multivariate logistic regression analysis illustrated that left atrial diameter (OR 1.201; 95% CI 1.093-1.320; P=0.000) and AC009509.2 (OR 1.732; 95% CI 1.092-2.747; P=0.020) were related to AF respectively. ROC curve showed that AC009509.2, LINC01781 and left atrial diameter (LAD) were predictors of AF. For LINC01781, the area under the curve (AUC) was 0.654 (95% CI 0.541-0.767, P=0.0113). For AC009509.2, the AUC was 0.710 (95% CI 0.599-0.822, P=0.0005). Bioinformatic methods (GO enrichment, AS analysis and lncRNA-mRNA network construction) were performed to reveal the role of lncRNAs. CONCLUSIONS: This study discussed differentially expressed lncRNA and their potential interaction with mRNA in AF. LncRNA AC009509.2 could be a new potential biomarker for AF prediction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-023-03573-5.
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spelling pubmed-106267012023-11-07 Identification of functional lncRNAs in atrial fibrillation based on RNA sequencing You, Yangyang Wang, Wei Zhu, Wenshu Xu, Jian BMC Cardiovasc Disord Research BACKGROUND: Atrial fibrillation (AF) is one of the most common arrhythmia contributing to serious conditions such as stroke and heart failure. Recent studies demonstrated that long noncoding RNAs (lncRNAs) were related to cardiovascular disease. However, the molecular mechanisms of AF are not fully clear. This study intended to discover lncRNAs that are differentially expressed in AF compared with controls and evaluate the potential functions of these lncRNAs. METHODS: Ninety-seven patients (49 patients with AF and 48 patients without AF) were included in this study. Among these patients, leucocyte suspensions of 3 AF patients and 3 controls were sent for RNA-seq analysis to select differentially expressed lncRNA and mRNA. Different lncRNA expressions were validated in another samples (46 AF patients and 45 controls). Gene ontology (GO) enrichment analysis was conducted to annotate the function of selected mRNAs. Alternative splicing (AS) analysis was performed and a lncRNA-mRNA network was also constructed. The receiver operating characteristics (ROC) curve was used to evaluate diagnostic values. Logistic regression analysis was utilized to assess the risk or protective factor of AF. RESULTS: A total of 223 mRNAs and 105 lncRNAs were detected in AF patients compared with controls. Total 4 lncRNAs (LINC01781, AC009509.2, AL662844.3, AL662844.4) associated with AF were picked out for validation in another samples by quantitative real-time PCR (qRT-PCR), detecting that upregulated AC009509.2 and downregulated LINC01781 in AF patients. Multivariate logistic regression analysis illustrated that left atrial diameter (OR 1.201; 95% CI 1.093-1.320; P=0.000) and AC009509.2 (OR 1.732; 95% CI 1.092-2.747; P=0.020) were related to AF respectively. ROC curve showed that AC009509.2, LINC01781 and left atrial diameter (LAD) were predictors of AF. For LINC01781, the area under the curve (AUC) was 0.654 (95% CI 0.541-0.767, P=0.0113). For AC009509.2, the AUC was 0.710 (95% CI 0.599-0.822, P=0.0005). Bioinformatic methods (GO enrichment, AS analysis and lncRNA-mRNA network construction) were performed to reveal the role of lncRNAs. CONCLUSIONS: This study discussed differentially expressed lncRNA and their potential interaction with mRNA in AF. LncRNA AC009509.2 could be a new potential biomarker for AF prediction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-023-03573-5. BioMed Central 2023-11-06 /pmc/articles/PMC10626701/ /pubmed/37932671 http://dx.doi.org/10.1186/s12872-023-03573-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
You, Yangyang
Wang, Wei
Zhu, Wenshu
Xu, Jian
Identification of functional lncRNAs in atrial fibrillation based on RNA sequencing
title Identification of functional lncRNAs in atrial fibrillation based on RNA sequencing
title_full Identification of functional lncRNAs in atrial fibrillation based on RNA sequencing
title_fullStr Identification of functional lncRNAs in atrial fibrillation based on RNA sequencing
title_full_unstemmed Identification of functional lncRNAs in atrial fibrillation based on RNA sequencing
title_short Identification of functional lncRNAs in atrial fibrillation based on RNA sequencing
title_sort identification of functional lncrnas in atrial fibrillation based on rna sequencing
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626701/
https://www.ncbi.nlm.nih.gov/pubmed/37932671
http://dx.doi.org/10.1186/s12872-023-03573-5
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