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Integrated Bioinformatics Analysis Confirms the Diagnostic Value of Nourin-Dependent miR-137 and miR-106b in Unstable Angina Patients

The challenge of rapidly diagnosing myocardial ischemia in unstable angina (UA) patients presenting to the Emergency Department (ED) is due to a lack of sensitive blood biomarkers. This has prompted an investigation into microRNAs (miRNAs) related to cardiac-derived Nourin for potential diagnostic a...

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Autores principales: Elgebaly, Salwa A., Peacock, W. Frank, Christenson, Robert H., Kreutzer, Donald L., Faraag, Ahmed Hassan Ibrahim, Sarguos, Amir Mahfouz Mokhtar, El-Khazragy, Nashwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573268/
https://www.ncbi.nlm.nih.gov/pubmed/37834231
http://dx.doi.org/10.3390/ijms241914783
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author Elgebaly, Salwa A.
Peacock, W. Frank
Christenson, Robert H.
Kreutzer, Donald L.
Faraag, Ahmed Hassan Ibrahim
Sarguos, Amir Mahfouz Mokhtar
El-Khazragy, Nashwa
author_facet Elgebaly, Salwa A.
Peacock, W. Frank
Christenson, Robert H.
Kreutzer, Donald L.
Faraag, Ahmed Hassan Ibrahim
Sarguos, Amir Mahfouz Mokhtar
El-Khazragy, Nashwa
author_sort Elgebaly, Salwa A.
collection PubMed
description The challenge of rapidly diagnosing myocardial ischemia in unstable angina (UA) patients presenting to the Emergency Department (ED) is due to a lack of sensitive blood biomarkers. This has prompted an investigation into microRNAs (miRNAs) related to cardiac-derived Nourin for potential diagnostic application. The Nourin protein is rapidly expressed in patients with acute coronary syndrome (ACS) (UA and acute myocardial infarction (AMI)). MicroRNAs regulate gene expression through mRNA binding and, thus, may represent potential biomarkers. We initially identified miR-137 and miR-106b and conducted a clinical validation, which demonstrated that they were highly upregulated in ACS patients, but not in healthy subjects and non-ACS controls. Using integrated comprehensive bioinformatics analysis, the present study confirms that the Nourin protein targets miR-137 and miR-106b, which are linked to myocardial ischemia and inflammation associated with ACS. Molecular docking demonstrated robust interactions between the Nourin protein and miR137/hsa-miR-106b, involving hydrogen bonds and hydrophobic interactions, with −10 kcal/mol binding energy. I-TASSER generated Nourin analogs, with the top 10 chosen for structural insights. Antigenic regions and MHCII epitopes within the Nourin SPGADGNGGEAMPGG sequence showed strong binding to HLA-DR/DQ alleles. The Cytoscape network revealed interactions of -miR137/hsa-miR--106b and Phosphatase and tensin homolog (PTEN) in myocardial ischemia. RNA Composer predicted the secondary structure of miR-106b. Schrödinger software identified key Nourin-RNA interactions critical for complex stability. The study identifies miR-137 and miR-106b as potential ACS diagnostic and therapeutic targets. This research underscores the potential of miRNAs targeting Nourin for precision ACS intervention. The analysis leverages RNA Composer, Schrödinger, and I-TASSER tools to explore interactions and structural insights. Robust Nourin-miRNA interactions are established, bolstering the case for miRNA-based interventions in ischemic injury. In conclusion, the study contributes to UA and AMI diagnosis strategies through bioinformatics-guided exploration of Nourin-targeting miRNAs. Supported by comprehensive molecular analysis, the hypoxia-induced miR-137 for cell apoptosis (a marker of cell damage) and the inflammation-induced miR-106b (a marker of inflammation) confirmed their potential clinical use as diagnostic biomarkers. This research reinforces the growing role of miR-137/hsa-miR-106b in the early diagnosis of myocardial ischemia in unstable angina patients.
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spelling pubmed-105732682023-10-14 Integrated Bioinformatics Analysis Confirms the Diagnostic Value of Nourin-Dependent miR-137 and miR-106b in Unstable Angina Patients Elgebaly, Salwa A. Peacock, W. Frank Christenson, Robert H. Kreutzer, Donald L. Faraag, Ahmed Hassan Ibrahim Sarguos, Amir Mahfouz Mokhtar El-Khazragy, Nashwa Int J Mol Sci Article The challenge of rapidly diagnosing myocardial ischemia in unstable angina (UA) patients presenting to the Emergency Department (ED) is due to a lack of sensitive blood biomarkers. This has prompted an investigation into microRNAs (miRNAs) related to cardiac-derived Nourin for potential diagnostic application. The Nourin protein is rapidly expressed in patients with acute coronary syndrome (ACS) (UA and acute myocardial infarction (AMI)). MicroRNAs regulate gene expression through mRNA binding and, thus, may represent potential biomarkers. We initially identified miR-137 and miR-106b and conducted a clinical validation, which demonstrated that they were highly upregulated in ACS patients, but not in healthy subjects and non-ACS controls. Using integrated comprehensive bioinformatics analysis, the present study confirms that the Nourin protein targets miR-137 and miR-106b, which are linked to myocardial ischemia and inflammation associated with ACS. Molecular docking demonstrated robust interactions between the Nourin protein and miR137/hsa-miR-106b, involving hydrogen bonds and hydrophobic interactions, with −10 kcal/mol binding energy. I-TASSER generated Nourin analogs, with the top 10 chosen for structural insights. Antigenic regions and MHCII epitopes within the Nourin SPGADGNGGEAMPGG sequence showed strong binding to HLA-DR/DQ alleles. The Cytoscape network revealed interactions of -miR137/hsa-miR--106b and Phosphatase and tensin homolog (PTEN) in myocardial ischemia. RNA Composer predicted the secondary structure of miR-106b. Schrödinger software identified key Nourin-RNA interactions critical for complex stability. The study identifies miR-137 and miR-106b as potential ACS diagnostic and therapeutic targets. This research underscores the potential of miRNAs targeting Nourin for precision ACS intervention. The analysis leverages RNA Composer, Schrödinger, and I-TASSER tools to explore interactions and structural insights. Robust Nourin-miRNA interactions are established, bolstering the case for miRNA-based interventions in ischemic injury. In conclusion, the study contributes to UA and AMI diagnosis strategies through bioinformatics-guided exploration of Nourin-targeting miRNAs. Supported by comprehensive molecular analysis, the hypoxia-induced miR-137 for cell apoptosis (a marker of cell damage) and the inflammation-induced miR-106b (a marker of inflammation) confirmed their potential clinical use as diagnostic biomarkers. This research reinforces the growing role of miR-137/hsa-miR-106b in the early diagnosis of myocardial ischemia in unstable angina patients. MDPI 2023-09-30 /pmc/articles/PMC10573268/ /pubmed/37834231 http://dx.doi.org/10.3390/ijms241914783 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Elgebaly, Salwa A.
Peacock, W. Frank
Christenson, Robert H.
Kreutzer, Donald L.
Faraag, Ahmed Hassan Ibrahim
Sarguos, Amir Mahfouz Mokhtar
El-Khazragy, Nashwa
Integrated Bioinformatics Analysis Confirms the Diagnostic Value of Nourin-Dependent miR-137 and miR-106b in Unstable Angina Patients
title Integrated Bioinformatics Analysis Confirms the Diagnostic Value of Nourin-Dependent miR-137 and miR-106b in Unstable Angina Patients
title_full Integrated Bioinformatics Analysis Confirms the Diagnostic Value of Nourin-Dependent miR-137 and miR-106b in Unstable Angina Patients
title_fullStr Integrated Bioinformatics Analysis Confirms the Diagnostic Value of Nourin-Dependent miR-137 and miR-106b in Unstable Angina Patients
title_full_unstemmed Integrated Bioinformatics Analysis Confirms the Diagnostic Value of Nourin-Dependent miR-137 and miR-106b in Unstable Angina Patients
title_short Integrated Bioinformatics Analysis Confirms the Diagnostic Value of Nourin-Dependent miR-137 and miR-106b in Unstable Angina Patients
title_sort integrated bioinformatics analysis confirms the diagnostic value of nourin-dependent mir-137 and mir-106b in unstable angina patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573268/
https://www.ncbi.nlm.nih.gov/pubmed/37834231
http://dx.doi.org/10.3390/ijms241914783
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