Journal
JOURNAL OF THE ROYAL SOCIETY INTERFACE
Volume 11, Issue 92, Pages -Publisher
ROYAL SOC
DOI: 10.1098/rsif.2013.1057
Keywords
Alzheimer's disease; bioinformatics; drug; microRNA; small molecule; therapeutics
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Funding
- National Natural Science Foundation of China [30900837]
- Heilongjiang Postdoctoral Funds for Scientific Research Initiation [LBH-Q11042]
- Graduate Innovation Fund of Heilongjiang Province [YJSCX2012-249HLJ]
- Program for Young Talents of Science and Technology in Harbin [2013RFQXJ057]
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Alzheimer's disease (AD) is an incurable neurodegenerative disorder. Much effort has been devoted to developing effective therapeutic agents. Recently, targeting microRNAs (miRNAs) with small molecules has become a novel therapy for human diseases. In this study, we present a systematic computational approach to construct a bioactive Small molecule and miRNA association Network in AD(SmiRN-AD), which is based on the gene expression signatures of bioactive small molecule perturbation and AD-related miRNA regulation. We also performed topological and functional analysis of the SmiRN-AD from multiple perspectives. At the significance level of p <= 0.01, 496 small molecule-miRNA associations, including 25 AD-related miRNAs and 275 small molecules, were recognized and used to construct the SmiRN-AD. The drugs that were connected with the same miRNA tended to share common drug targets (p = 1.72 x 10(-4)) and belong to the same therapeutic category (p = 4.22 x 10(-8)). The miRNAs that were linked to the same small molecule regulated more common miRNA targets (p = 6.07 x 10(-3)). Further analysis of the positive connections (quinostatin and miR-148b, amantadine and miR-15a) and the negative connections (melatonin and miR-30e-5p) indicated that our large-scale predictions afforded specific biological insights into AD pathogenesis and therapy. This study proposes a holistic strategy for deciphering the associations between small molecules and miRNAs in AD, which may be helpful for developing a novel effective miRNA-associated therapeutic strategy for AD. A comprehensive database for the SmiRN-AD and the differential expression patterns of the miRNA targets in AD is freely available at http://bioinfo.hrbmu.edu.cn/SmiRN-AD/.
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