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miR-208b Reduces the Expression of Kcnj5 in a Cardiomyocyte Cell Line

MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among them cardiac hypertrophy and atrial fibrillation. Cardiac miR expression was analyzed in a mouse model with structural and electrical remodeling. Next-generation sequencing revealed that miR-208b-3p was ~25-fold upre...

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Autores principales: Hupfeld, Julia, Ernst, Maximilian, Knyrim, Maria, Binas, Stephanie, Kloeckner, Udo, Rabe, Sindy, Quarch, Katja, Misiak, Danny, Fuszard, Matthew, Grossmann, Claudia, Gekle, Michael, Schreier, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301481/
https://www.ncbi.nlm.nih.gov/pubmed/34201741
http://dx.doi.org/10.3390/biomedicines9070719
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author Hupfeld, Julia
Ernst, Maximilian
Knyrim, Maria
Binas, Stephanie
Kloeckner, Udo
Rabe, Sindy
Quarch, Katja
Misiak, Danny
Fuszard, Matthew
Grossmann, Claudia
Gekle, Michael
Schreier, Barbara
author_facet Hupfeld, Julia
Ernst, Maximilian
Knyrim, Maria
Binas, Stephanie
Kloeckner, Udo
Rabe, Sindy
Quarch, Katja
Misiak, Danny
Fuszard, Matthew
Grossmann, Claudia
Gekle, Michael
Schreier, Barbara
author_sort Hupfeld, Julia
collection PubMed
description MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among them cardiac hypertrophy and atrial fibrillation. Cardiac miR expression was analyzed in a mouse model with structural and electrical remodeling. Next-generation sequencing revealed that miR-208b-3p was ~25-fold upregulated. Therefore, the aim of our study was to evaluate the impact of miR-208b on cardiac protein expression. First, an undirected approach comparing whole RNA sequencing data to miR-walk 2.0 miR-208b 3′-UTR targets revealed 58 potential targets of miR-208b being regulated. We were able to show that miR-208b mimics bind to the 3′ untranslated region (UTR) of voltage-gated calcium channel subunit alpha1 C and Kcnj5, two predicted targets of miR-208b. Additionally, we demonstrated that miR-208b mimics reduce GIRK1/4 channel-dependent thallium ion flux in HL-1 cells. In a second undirected approach we performed mass spectrometry to identify the potential targets of miR-208b. We identified 40 potential targets by comparison to miR-walk 2.0 3′-UTR, 5′-UTR and CDS targets. Among those targets, Rock2 and Ran were upregulated in Western blots of HL-1 cells by miR-208b mimics. In summary, miR-208b targets the mRNAs of proteins involved in the generation of cardiac excitation and propagation, as well as of proteins involved in RNA translocation (Ran) and cardiac hypertrophic response (Rock2).
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spelling pubmed-83014812021-07-24 miR-208b Reduces the Expression of Kcnj5 in a Cardiomyocyte Cell Line Hupfeld, Julia Ernst, Maximilian Knyrim, Maria Binas, Stephanie Kloeckner, Udo Rabe, Sindy Quarch, Katja Misiak, Danny Fuszard, Matthew Grossmann, Claudia Gekle, Michael Schreier, Barbara Biomedicines Article MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among them cardiac hypertrophy and atrial fibrillation. Cardiac miR expression was analyzed in a mouse model with structural and electrical remodeling. Next-generation sequencing revealed that miR-208b-3p was ~25-fold upregulated. Therefore, the aim of our study was to evaluate the impact of miR-208b on cardiac protein expression. First, an undirected approach comparing whole RNA sequencing data to miR-walk 2.0 miR-208b 3′-UTR targets revealed 58 potential targets of miR-208b being regulated. We were able to show that miR-208b mimics bind to the 3′ untranslated region (UTR) of voltage-gated calcium channel subunit alpha1 C and Kcnj5, two predicted targets of miR-208b. Additionally, we demonstrated that miR-208b mimics reduce GIRK1/4 channel-dependent thallium ion flux in HL-1 cells. In a second undirected approach we performed mass spectrometry to identify the potential targets of miR-208b. We identified 40 potential targets by comparison to miR-walk 2.0 3′-UTR, 5′-UTR and CDS targets. Among those targets, Rock2 and Ran were upregulated in Western blots of HL-1 cells by miR-208b mimics. In summary, miR-208b targets the mRNAs of proteins involved in the generation of cardiac excitation and propagation, as well as of proteins involved in RNA translocation (Ran) and cardiac hypertrophic response (Rock2). MDPI 2021-06-23 /pmc/articles/PMC8301481/ /pubmed/34201741 http://dx.doi.org/10.3390/biomedicines9070719 Text en © 2021 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
Hupfeld, Julia
Ernst, Maximilian
Knyrim, Maria
Binas, Stephanie
Kloeckner, Udo
Rabe, Sindy
Quarch, Katja
Misiak, Danny
Fuszard, Matthew
Grossmann, Claudia
Gekle, Michael
Schreier, Barbara
miR-208b Reduces the Expression of Kcnj5 in a Cardiomyocyte Cell Line
title miR-208b Reduces the Expression of Kcnj5 in a Cardiomyocyte Cell Line
title_full miR-208b Reduces the Expression of Kcnj5 in a Cardiomyocyte Cell Line
title_fullStr miR-208b Reduces the Expression of Kcnj5 in a Cardiomyocyte Cell Line
title_full_unstemmed miR-208b Reduces the Expression of Kcnj5 in a Cardiomyocyte Cell Line
title_short miR-208b Reduces the Expression of Kcnj5 in a Cardiomyocyte Cell Line
title_sort mir-208b reduces the expression of kcnj5 in a cardiomyocyte cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301481/
https://www.ncbi.nlm.nih.gov/pubmed/34201741
http://dx.doi.org/10.3390/biomedicines9070719
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