机构：[1]Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.[2]State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.四川大学华西医院[3]Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.[4]Center for Complex Networks Research, Northeastern University, Boston, USA.
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/.
基金：
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：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|1 区医学
小类|2 区细胞生物学2 区肿瘤学
最新[2023]版：
无
第一作者：
第一作者机构：[1]Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
通讯作者：
通讯机构：[2]State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.[3]Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.[4]Center for Complex Networks Research, Northeastern University, Boston, USA.
推荐引用方式(GB/T 7714)：
Li Jie,Lei Kecheng,Wu Zengrui,et al.Network-based identification of microRNAs as potential pharmacogenomic biomarkers for anticancer drugs.[J].Oncotarget.2016,7(29):45584-45596.doi:10.18632/oncotarget.10052.
APA：
Li Jie,Lei Kecheng,Wu Zengrui,Li Weihua,Liu Guixia...&Tang Yun.(2016).Network-based identification of microRNAs as potential pharmacogenomic biomarkers for anticancer drugs..Oncotarget,7,(29)
MLA：
Li Jie,et al."Network-based identification of microRNAs as potential pharmacogenomic biomarkers for anticancer drugs.".Oncotarget 7..29(2016):45584-45596
医学