Research Paper Volume 8, Issue 2 pp 272—290
Primate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer's disease
- 1 Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education, National Health and Family Planning Commission, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
- 2 Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
- 3 PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China
- 4 Brainnetome Center, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
Received: January 5, 2016 Accepted: January 20, 2016 Published: February 8, 2016
https://doi.org/10.18632/aging.100887How to Cite
Abstract
Alzheimer's disease (AD) is a serious neurodegenerative disease, and microRNAs (miRNAs) have been linked to its pathogenesis. miR-603, a novel primate-specific miRNA and an intronic miRNA of a human brain highly expressed gene KIAA1217, is implicated in the risk and pathogenesis of AD. The rs11014002 single nucleotide polymorphism (SNP) (C/U), which locates in miR-603 precursor (pre-miR-603), exhibits a protective effect towards AD risk. Additionally, the rs11014002 SNP promotes the biogenesis of mature miR-603. miR-603 downregulates LRPAP1 mRNA and protein levels through directly binding the 3′ untranslated region (3′UTR) of LRPAP1. Moreover, miR-603 increases LRP1 protein expression. LRPAP1 and LRP1, playing opposite roles, are involved in Aβ clearance and pathogenesis of AD. Strikingly, miR-603 exhibits a relatively higher expression and there is a loss of a negative correlation between miR-603 and LRPAP1/RND1 mRNA levels in the hippocampi of patients with AD. In addition, miR-603 directly downregulates a key neuronal apoptotic component-E2F1, and prevents HeLa cells from undergoing H2O2-induced apoptosis. This work suggests that miR-603 may be a novel AD-relevant miRNA and that its rs11014002 SNP may serve as a protective factor against AD.