title: MicroRNA-103-1 selectively downregulates brain NCX1 and its inhibition by anti-miRNA ameliorates stroke damage and neurological deficits.
abstract: Na(+)/Ca2+ exchanger (NCX) is a plasma membrane transporter that, by regulating Ca2+ and Na(+) homeostasis, contributes to brain stroke damage. The objectives of this study were to investigate whether there might be miRNAs in the brain able to regulate NCX1 expression and, thereafter, to set up a valid therapeutic strategy able to reduce stroke-induced brain damage by regulating NCX1 expression. Thus, we tested whether miR-103-1, a microRNA belonging to the miR-103/107 family that on the basis of sequence analysis might be a potential NCX1 regulator, could control NCX1 expression. The role of miR-103-1 was assessed in a rat model of transient cerebral ischemia by evaluating the effect of the correspondent antimiRNA on both brain infarct volume and neurological deficits. NCX1 expression was dramatically reduced when cortical neurons were exposed to miR-103-1. This alleged tight regulation of NCX1 by miR-103-1 was further corroborated by luciferase assay. Notably, antimiR-103-1 prevented NCX1 protein downregulation induced by the increase in miR-103-1 after brain ischemia, thereby reducing brain damage and neurological deficits. Overall, the identification of a microRNA able to selectively regulate NCX1 in the brain clarifies a new important molecular mechanism of NCX1 regulation in the brain and offers the opportunity to develop a new therapeutic strategy for stroke.
authors: Division of Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Antonio
authors: A
authors: Vinciguerra
authors: 1] Division of Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy [2] Department of Biological and Environmental Sciences, University of Sannio, Benevento, Italy.
authors: Luigi
authors: L
authors: Formisano
authors: Division of Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Pierpaolo
authors: P
authors: Cerullo
authors: Division of Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Natascia
authors: N
authors: Guida
authors: Division of Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Ornella
authors: O
authors: Cuomo
authors: Division of Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Alba
authors: A
authors: Esposito
authors: Division of Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Gianfranco
authors: G
authors: Di Renzo
authors: 1] Division of Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy [2] IRCCS Fondazione SDN, Naples, Italy.
authors: Lucio
authors: L
authors: Annunziato
authors: Division of Pharmacology, Department Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy.
authors: Giuseppe
authors: G
authors: Pignataro
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D015536:Down-Regulation; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D020320:Oligoribonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D034622:RNA Interference; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000737:chemistry / Q000235:genetics*; D020521:Stroke / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C544749:MIRN103 microRNA, human; D035683:MicroRNAs; D020320:Oligoribonucleotides, Antisense; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1