title: microRNA-181a is involved in insulin-like growth factor-1-mediated regulation of the transcription factor CREB1.
abstract: microRNAs are a class of small non-coding RNA molecules negatively regulating gene expression at post-transcriptional level in many tissues including the central nervous system. cAMP response element binding protein (CREB) is a key nuclear factor highly expressed in hippocampal neurons on which many signal pathways converge. Recent studies have found that microRNA-181a is rich in mature nerve cells, and bioinformatics analysis shows that the CREB1 mRNA 3'-untranslated region (3'UTR) contains complementary sequence to the miR-181a seed region. In this study, we investigated whether miR-181a is a negative regulator for CREB1 expression in neurons. It was found that the expression of miR-181a was negatively correlated with Insulin-like growth factor-1 (IGF-1) and CREB1 in the Lewis rat hippocampus. miR-181a bound to CREB1 mRNA through a specific binding site in the 3'UTR sequence. The expression of CREB1 in PC12 cells was down-regulated by transfection with a miR-181a mimic and up-regulated by a miR-181a inhibitor. A down-regulated miR-181a and an up-regulated CREB1 were observed in IGF-1-stimulated PC12 cells. And miR-181a inhibited dendritic growth of cultured hippocampus neurons. These suggest that miR-181a is involved in IGF-1-regulated CREB1 expression by targeting its mRNA 3'UTR. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and are involved in the central nervous system development. Here, we demonstrate that miR-181a can inhibit the expression of the transcription factor CREB1 by specifically targeting its mRNA 3'UTR and inhibit the development of hippocampus neurons. Repressed expression of miR-181a is involved in IGF-1-mediated up-regulation of CREB1 in vivo and in vitro. These findings indicate that miR-181a could be a potential target for preventing neurodegenerative diseases.
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhao
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Yimei
authors.initials: Y
authors.lastname: Gao
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D019295:Computational Biology; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis* / Q000235:genetics*; D003712:Dendrites / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter; D005822:Genetic Vectors; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D046228:Microarray Analysis; D016716:PC12 Cells; D011247:Pregnancy; D051381:Rats; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; C581717:MIRN181 microRNA, rat; D035683:MicroRNAs; D007334:Insulin-Like Growth Factor I; D008156:Luciferases
keywords: CREB1; IGF-1; PC12 cells; hippocampus; miR-181a