title: MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke.
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.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Jun Rong
authors.initials: JR
authors.lastname: Tan
authors.affiliation: Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kay Sin
authors.initials: KS
authors.lastname: Tan
authors.affiliation: Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: Fung Lin
authors.initials: FL
authors.lastname: Yong
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Arunmozhiarasi
authors.initials: A
authors.lastname: Armugam
authors.affiliation: Department of Biochemistry, Faculty of Medicine, MAHSA University, Kuala Lumpur, Malaysia.
authors.forename: Chee Woon
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Kandiah
authors.initials: K
authors.lastname: Jeyaseelan
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, MD3, Singapore.
authors.forename: Peter Tsun-Hon
authors.initials: PT
authors.lastname: Wong
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D017930:Genes, Reporter; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051916:Membrane Cofactor Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012372:ROC Curve; D016415:Sequence Alignment; D020521:Stroke / Q000235:genetics / Q000473:pathology*
chemical_list: D020413:3' Untranslated Regions; D051916:Membrane Cofactor Protein; D035683:MicroRNAs