microRNA-128a dysregulation in transgenic Huntington’s disease monkeys

• Type of Material: Article
• Authors: Jannet Kocerha, Yerkes National Primate Research Center; Yan Xu, Yerkes National Primate Research Center; Melinda S Prucha, Yerkes National Primate Research Center; Dongming Zhao, Yerkes National Primate Research Center; Anthony Chan, Emory University
• Language: English
• Date: 2014
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Kocerha et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://www.molecularbrain.com/content/7/1/46
• Title of Journal or Parent Work: Molecular Brain
• ISSN: 1756-6606
• Volume: 7
• Issue: 46
• Grant/Funding Information: This work was supported by grants awarded to AWSC by ORIP/NIH (RR018827) and the American Recovery and Reinvestment Act (ARRA) Fund).; The YNPRC is supported by the base grant P51RR165 awarded by the Animal Resources Program of the NIH.
• Keywords: microRNAs; Brain; Huntington’s disease; miR-128a; Noncoding RNAs
• Research Categories: Biology, Zoology; Biology, Genetics

Abstract

Background Huntington’s Disease (HD) is a progressive neurodegenerative disorder with a single causal mutation in the Huntingtin (HTT) gene. MicroRNAs (miRNAs) have recently been implicated as epigenetic regulators of neurological disorders, however, their role in HD pathogenesis is not well defined. Here we study transgenic HD monkeys (HD monkeys) to examine miRNA dysregulation in a primate model of the disease. Results In this report, 11 miRNAs were found to be significantly associated (P value < 0.05) with HD in the frontal cortex of the HD monkeys. We further focused on one of those candidates, miR-128a, due to the corresponding disruption in humans and mice with HD as well as its intriguing lists of gene targets. miR-128a was downregulated in our HD monkey model by the time of birth. We then confirmed that miR-128a was also downregulated in the brains of pre-symptomatic and post-symptomatic HD patients. Additionally, our studies confirmed a panel of canonical HD signaling genes regulated by miR-128a, including HTT and Huntingtin Interaction Protein 1 (HIP1). Conclusion Our studies found that miR-128a may play a critical role in HD and could be a viable candidate as a therapeutic or biomarker of the disease.