MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke

Ischemic stroke is a major cause of mortality and morbidity globally. Among the ischemic stroke subtypes, cardioembolic stroke is with poor functional outcome (Modified Rankin score ≥ 2). Early diagnosis of cardioembolic stroke will prove beneficial. This study examined the microRNAs targeting clust...

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Autores principales: Tan, J.R., Tan, K.S., Yong, F.L., Armugam, A., Wang, C.W., Jeyaseelan, K., Wong, P.T.H.
Formato: Artículo
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:http://eprints.um.edu.my/19010/1/MicroRNAs_regulating_cluster_of_differentiation_46_%28CD46%29_in_cardioembolic_and_non-cardioembolic_stroke.pdf
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author Tan, J.R.
Tan, K.S.
Yong, F.L.
Armugam, A.
Wang, C.W.
Jeyaseelan, K.
Wong, P.T.H.
author_facet Tan, J.R.
Tan, K.S.
Yong, F.L.
Armugam, A.
Wang, C.W.
Jeyaseelan, K.
Wong, P.T.H.
author_sort Tan, J.R.
collection UM
description Ischemic stroke is a major cause of mortality and morbidity globally. Among the ischemic stroke subtypes, cardioembolic stroke is with poor functional outcome (Modified Rankin score ≥ 2). Early diagnosis of cardioembolic stroke will prove beneficial. This study examined the microRNAs targeting cluster of differentiation 46 (CD46), a potential biomarker for cardioembolic stroke. CD46 mRNA level was shown to be differentially expressed (p < 0.001) between cardioembolic stroke (median = 1.32) and non-cardioembolic stroke subtypes (large artery stroke median = 5.05; small vessel stroke median = 6.45). Bioinformatic search showed that miR-19a, -20a, -185 and -374b were found to target CD46 mRNA and further verified by luciferase reporter assay. The levels of miRNAs targeting CD46 were significantly reduced (p < 0.05) in non-cardioembolic stroke patients (large artery stroke median: miR-19a = 0.63, miR-20a = 0.42, miR-185 = 0.32, miR-374b = 0.27; small artery stroke median: miR-19a = 0.07, miR-20a = 0.06, miR-185 = 0.07, miR-374b = 0.05) as compared to cardioembolic stroke patients (median: miR-19a = 2.69, miR-20a = 1.36, miR-185 = 1.05, miR-374b = 1.23). ROC curve showed that the miRNAs could distinguish cardioembolic stroke from non-cardioembolic stroke with better AUC value as compared to CD46. Endogenous expression of CD46 in Human Umbilical Vein Endothelial Cells (HUVECs) were found to be regulated by miR-19a and miR-20a. Thus implicating that miR-19a and -20a may play a role in pathogenesis of cardioembolic stroke, possibly via the endothelial cells.
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spelling um.eprints-190102018-08-10T09:06:37Z http://eprints.um.edu.my/19010/ MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke Tan, J.R. Tan, K.S. Yong, F.L. Armugam, A. Wang, C.W. Jeyaseelan, K. Wong, P.T.H. R Medicine Ischemic stroke is a major cause of mortality and morbidity globally. Among the ischemic stroke subtypes, cardioembolic stroke is with poor functional outcome (Modified Rankin score ≥ 2). Early diagnosis of cardioembolic stroke will prove beneficial. This study examined the microRNAs targeting cluster of differentiation 46 (CD46), a potential biomarker for cardioembolic stroke. CD46 mRNA level was shown to be differentially expressed (p < 0.001) between cardioembolic stroke (median = 1.32) and non-cardioembolic stroke subtypes (large artery stroke median = 5.05; small vessel stroke median = 6.45). Bioinformatic search showed that miR-19a, -20a, -185 and -374b were found to target CD46 mRNA and further verified by luciferase reporter assay. The levels of miRNAs targeting CD46 were significantly reduced (p < 0.05) in non-cardioembolic stroke patients (large artery stroke median: miR-19a = 0.63, miR-20a = 0.42, miR-185 = 0.32, miR-374b = 0.27; small artery stroke median: miR-19a = 0.07, miR-20a = 0.06, miR-185 = 0.07, miR-374b = 0.05) as compared to cardioembolic stroke patients (median: miR-19a = 2.69, miR-20a = 1.36, miR-185 = 1.05, miR-374b = 1.23). ROC curve showed that the miRNAs could distinguish cardioembolic stroke from non-cardioembolic stroke with better AUC value as compared to CD46. Endogenous expression of CD46 in Human Umbilical Vein Endothelial Cells (HUVECs) were found to be regulated by miR-19a and miR-20a. Thus implicating that miR-19a and -20a may play a role in pathogenesis of cardioembolic stroke, possibly via the endothelial cells. Public Library of Science 2017 Article PeerReviewed application/pdf en http://eprints.um.edu.my/19010/1/MicroRNAs_regulating_cluster_of_differentiation_46_%28CD46%29_in_cardioembolic_and_non-cardioembolic_stroke.pdf Tan, J.R. and Tan, K.S. and Yong, F.L. and Armugam, A. and Wang, C.W. and Jeyaseelan, K. and Wong, P.T.H. (2017) MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke. PLoS ONE, 12 (2). e0172131. ISSN 1932-6203, DOI https://doi.org/10.1371/journal.pone.0172131 <https://doi.org/10.1371/journal.pone.0172131>. http://dx.doi.org/10.1371/journal.pone.0172131 doi:10.1371/journal.pone.0172131
spellingShingle R Medicine
Tan, J.R.
Tan, K.S.
Yong, F.L.
Armugam, A.
Wang, C.W.
Jeyaseelan, K.
Wong, P.T.H.
MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke
title MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke
title_full MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke
title_fullStr MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke
title_full_unstemmed MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke
title_short MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke
title_sort micrornas regulating cluster of differentiation 46 cd46 in cardioembolic and non cardioembolic stroke
topic R Medicine
url http://eprints.um.edu.my/19010/1/MicroRNAs_regulating_cluster_of_differentiation_46_%28CD46%29_in_cardioembolic_and_non-cardioembolic_stroke.pdf
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