Identification of associations between small molecule drugs and miRNAs based on functional similarity
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Jing Wang1,*, Fanlin Meng1,*, EnYu Dai1, Feng Yang1, Shuyuan Wang1, Xiaowen Chen1, Lei Yang1, Yuwen Wang2, Wei Jiang1
1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, P. R. China
2The 2nd Affiliated Hospital, Harbin Medical University, Harbin 150081, P. R. China
*These authors have contributed equally to this work
Wei Jiang, email: [email protected]
Keywords: small molecule, miRNA, drug, functional similarity, microarray
Received: November 26, 2015 Accepted: May 08, 2016 Published: May 24, 2016
MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate gene expression at post-transcriptional level. Increasing evidences show aberrant expression of miRNAs in varieties of diseases. Targeting the dysregulated miRNAs with small molecule drugs has become a novel therapy for many human diseases, especially cancer. Here, we proposed a novel computational approach to identify associations between small molecules and miRNAs based on functional similarity of differentially expressed genes. At the significance level of p < 0.01, we constructed the small molecule and miRNA functional similarity network involving 111 small molecules and 20 miRNAs. Moreover, we also predicted associations between drugs and diseases through integrating our identified small molecule-miRNA associations with experimentally validated disease related miRNAs. As a result, we identified 2265 associations between FDA approved drugs and diseases, in which ~35% associations have been validated by comprehensive literature reviews. For breast cancer, we identified 19 potential drugs, in which 12 drugs were supported by previous studies. In addition, we performed survival analysis for the patients from TCGA and GEO database, which indicated that the associated miRNAs of 4 drugs might be good prognosis markers in breast cancer. Collectively, this study proposed a novel approach to predict small molecule and miRNA associations based on functional similarity, which may pave a new way for miRNA-targeted therapy and drug repositioning.
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