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Research Paper|Volume 8, Issue 2|pp 272—290

Primate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer's disease

Chi Zhang1, Jie Lu1, Bing Liu4, Qinghua Cui2, Yun Wang1,3
  • 1Neuroscience 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
  • 2Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
  • 3PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China
  • 4Brainnetome Center, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China

* * Equal contribution

Received: January 5, 2016Accepted: January 20, 2016Published: February 8, 2016
https://doi.org/10.18632/aging.100887

Copyright: © 2016 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.