文献类型：期刊文献

英文题名：Network-based identification of microRNAs as potential pharmacogenomic biomarkers for anticancer drugs

作者：Li, Jie[1];Lei, Kecheng[1];Wu, Zengrui[1];Li, Weihua[1];Liu, Guixia[1];Liu, Jianwen[1];Cheng, Feixiong[2,3,4];Tang, Yun[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[2]Sichuan Univ, West China Med Sch, West China Hosp, Collaborat Innovat Ctr Biotherapy,State Key Lab B, Chengdu, Peoples R China;[3]Harvard Med Sch, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA USA;[4]Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA

年份：2016

卷号：7

期号：29

起止页码：45584

外文期刊名：ONCOTARGET

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000385402300057)】；

基金：This work was supported by the National Natural Science Foundation of China (Grant 81373329 and 81573020), the 863 Project (Grant 2012AA020308), the Fundamental Research Funds for the Central Universities (Grant WY1113007), and the 111 Project (Grant B07023).

语种：英文

外文关键词：pharmacogenomics; miRNA; network-based inference; metformin; breast cancer

摘要：As the recent development of high-throughput technologies in cancer pharmacogenomics, there is an urgent need to develop new computational approaches for comprehensive identification of new pharmacogenomic biomarkers, such as microRNAs (miRNAs). In this study, a network-based framework, namely the SMiR-NBI model, was developed to prioritize miRNAs as potential biomarkers characterizing treatment responses of anticancer drugs on the basis of a heterogeneous network connecting drugs, miRNAs and genes. A high area under the receiver operating characteristic curve of 0.820 +/- 0.013 was yielded during 10-fold cross validation. In addition, high performance was further validated in identifying new anticancer mechanism-of-action for natural products and non-steroidal anti-inflammatory drugs. Finally, the newly predicted miRNAs for tamoxifen and metformin were experimentally validated in MCF-7 and MDA-MB-231 breast cancer cell lines via qRT-PCR assays. High success rates of 60% and 65% were yielded for tamoxifen and metformin, respectively. Specifically, 11 oncomiRNAs (e.g. miR-20a-5p, miR-27a-3p, miR-29a-3p, and miR-146a-5p) from the top 20 predicted miRNAs were experimentally verified as new pharmacogenomic biomarkers for metformin in MCF-7 or MDA-MB-231 cell lines. In summary, the SMiR-NBI model would provide a powerful tool to identify potential pharmacogenomic biomarkers characterized by miRNAs in the emerging field of precision cancer medicine, which is available at http://lmmd.ecust.edu.cn/database/smir-nbi/.