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

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.

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Abstract

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.

Item Type:	Article
Funders:	National Research Foundation (NRF): R-184-002-165-281, National Medical Research Council (NMRC/EDG): R-183-000-230-275, National Medical Research Council (NMRC/IRG): R-183-000-290-213, Singapore, University of Malaya (UM/HIR): E0067 & E0036
Uncontrolled Keywords:	3' Untranslated Regions; Adult; Aged; Aged, 80 and over; Antigens, CD46; Area Under Curve; Base Sequence; Case-Control Studies; Female; Genes, Reporter; Human Umbilical Vein Endothelial Cells; Humans; Male; MicroRNAs; Middle Aged; ROC Curve; Sequence Alignment; Stroke
Subjects:	R Medicine
Divisions:	Faculty of Medicine
Depositing User:	Ms. Juhaida Abd Rahim
Date Deposited:	10 Aug 2018 09:06
Last Modified:	10 Aug 2018 09:06
URI:	http://eprints.um.edu.my/id/eprint/19010

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