{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:30:03Z","timestamp":1775277003482,"version":"3.50.1"},"reference-count":91,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T00:00:00Z","timestamp":1549843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["NE2018101"],"award-info":[{"award-number":["NE2018101"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Foundation for the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["61571169"],"award-info":[{"award-number":["61571169"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug repositioning has become a prevailing tactic as this strategy is efficient, economical and low risk for drug discovery. Meanwhile, recent studies have confirmed that small-molecule drugs can modulate the expression of disease-related miRNAs, which indicates that miRNAs are promising therapeutic targets for complex diseases. In this study, we put forward and verified the hypothesis that drugs with similar miRNA profiles may share similar therapeutic properties. Furthermore, a comprehensive drug\u2013drug interaction network was constructed based on curated drug-miRNA associations. Through random network comparison, topological structure analysis and network module extraction, we found that the closely linked drugs in the network tend to treat the same diseases. Additionally, the curated drug\u2013disease relationships (from the CTD) and random walk with restarts algorithm were utilized on the drug\u2013drug interaction network to identify the potential drugs for a given disease. Both internal validation (leave-one-out cross-validation) and external validation (independent drug\u2013disease data set from the ChEMBL) demonstrated the effectiveness of the proposed approach. Finally, by integrating drug-miRNA and miRNA-disease information, we also explain the modes of action of drugs in the view of miRNA regulation. In summary, our work could determine novel and credible drug indications and offer novel insights and valuable perspectives for drug repositioning.<\/jats:p>","DOI":"10.1093\/bib\/bbz012","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T12:06:53Z","timestamp":1547467613000},"page":"498-510","source":"Crossref","is-referenced-by-count":28,"title":["In silico drug repositioning based on drug-miRNA associations"],"prefix":"10.1093","volume":"21","author":[{"given":"Xu","family":"Zhou","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China"}]},{"given":"Enyu","family":"Dai","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China"}]},{"given":"Qian","family":"Song","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China"}]},{"given":"Xueyan","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China"}]},{"given":"Qianqian","family":"Meng","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China"}]},{"given":"Yongshuai","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, P. R. China"}]}],"member":"286","published-online":{"date-parts":[[2019,2,11]]},"reference":[{"key":"2020080709362928700_ref1","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1377\/hlthaff.25.2.420","article-title":"Estimating the cost of new drug development: is it really 802 million dollars?","volume":"25","author":"Adams","year":"2006","journal-title":"Health Aff (Millwood)"},{"key":"2020080709362928700_ref2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0167-6296(02)00126-1","article-title":"The price of innovation: new estimates of drug development costs","volume":"22","author":"DiMasi","year":"2003","journal-title":"J Health Econ"},{"key":"2020080709362928700_ref3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/bib\/bbv020","article-title":"A survey of current trends in computational drug repositioning","volume":"17","author":"Li","year":"2016","journal-title":"Brief Bioinform"},{"key":"2020080709362928700_ref4","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1038\/4243","article-title":"Protein-site targeting. Diversification of the drug discovery process","volume":"16","author":"Krantz","year":"1998","journal-title":"Nat Biotechnol"},{"key":"2020080709362928700_ref5","first-page":"1394","article-title":"Drug discovery","volume":"324","author":"Boguski","year":"2009","journal-title":"Repurposing with a difference. Science"},{"key":"2020080709362928700_ref6","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nrd1468","article-title":"Drug repositioning: identifying and developing new uses for existing drugs","volume":"3","author":"Ashburn","year":"2004","journal-title":"Nat Rev Drug Discov"},{"key":"2020080709362928700_ref7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0735-1097(00)00705-1","article-title":"Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina","volume":"36","author":"Webb","year":"2000","journal-title":"J Am Coll Cardiol"},{"key":"2020080709362928700_ref8","first-page":"47","article-title":"Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction","volume":"8","author":"Boolell","year":"1996","journal-title":"Int J Impot Res"},{"key":"2020080709362928700_ref9","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nrd2030","article-title":"Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond","volume":"5","author":"Ghofrani","year":"2006","journal-title":"Nat Rev Drug Discov"},{"key":"2020080709362928700_ref10","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1093\/bib\/bbr013","article-title":"Exploiting drug\u2013disease relationships for computational drug repositioning","volume":"12","author":"Dudley","year":"2011","journal-title":"Brief Bioinform"},{"key":"2020080709362928700_ref11","doi-asserted-by":"crossref","first-page":"W137","DOI":"10.1093\/nar\/gku412","article-title":"DiseaseConnect: a comprehensive web server for mechanism-based disease\u2013disease connections","volume":"42","author":"Liu","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2020080709362928700_ref12","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1124\/jpet.110.165860","article-title":"Pharmacological foundations of cardio-oncology","volume":"334","author":"Minotti","year":"2010","journal-title":"J Pharmacol Exp Ther"},{"key":"2020080709362928700_ref13","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1136\/thx.2007.086819","article-title":"Obesity and the lung: 4","volume":"63","author":"Sin","year":"2008","journal-title":"Obesity and asthma. Thorax"},{"key":"2020080709362928700_ref14","doi-asserted-by":"crossref","first-page":"R91","DOI":"10.1186\/gb-2009-10-9-r91","article-title":"Genome-wide prioritization of disease genes and identification of disease\u2013disease associations from an integrated human functional linkage network","volume":"10","author":"Linghu","year":"2009","journal-title":"Genome Biol"},{"key":"2020080709362928700_ref15","doi-asserted-by":"crossref","first-page":"8685","DOI":"10.1073\/pnas.0701361104","article-title":"The human disease network","volume":"104","author":"Goh","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020080709362928700_ref16","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.1093\/bioinformatics\/btv474","article-title":"DSviaDRM: an R package for estimating disease similarity via dysfunctional regulation mechanism","volume":"31","author":"Yang","year":"2015","journal-title":"Bioinformatics"},{"key":"2020080709362928700_ref17","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/clpt.2009.103","article-title":"Systematic evaluation of drug\u2013disease relationships to identify leads for novel drug uses","volume":"86","author":"Chiang","year":"2009","journal-title":"Clin Pharmacol Ther"},{"key":"2020080709362928700_ref18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0006536","article-title":"Human disease\u2013drug network based on genomic expression profiles","volume":"4","author":"Hu","year":"2009","journal-title":"PLoS One"},{"key":"2020080709362928700_ref19","doi-asserted-by":"crossref","first-page":"i232","DOI":"10.1093\/bioinformatics\/btn162","article-title":"Prediction of drug\u2013target interaction networks from the integration of chemical and genomic spaces","volume":"24","author":"Yamanishi","year":"2008","journal-title":"Bioinformatics"},{"key":"2020080709362928700_ref20","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1002503","article-title":"Prediction of drug\u2013target interactions and drug repositioning via network-based inference","volume":"8","author":"Cheng","year":"2012","journal-title":"PLoS Comput Biol"},{"key":"2020080709362928700_ref21","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1126\/science.1158140","article-title":"Drug target identification using side-effect similarity","volume":"321","author":"Campillos","year":"2008","journal-title":"Science"},{"key":"2020080709362928700_ref22","doi-asserted-by":"crossref","first-page":"14621","DOI":"10.1073\/pnas.1000138107","article-title":"Discovery of drug mode of action and drug repositioning from transcriptional responses","volume":"107","author":"Iorio","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020080709362928700_ref23","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1126\/science.1132939","article-title":"The connectivity map: using gene-expression signatures to connect small molecules, genes, and disease","volume":"313","author":"Lamb","year":"2006","journal-title":"Science"},{"key":"2020080709362928700_ref24","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1093\/bioinformatics\/btv055","article-title":"Similarity-based prediction for anatomical therapeutic chemical classification of drugs by integrating multiple data sources","volume":"31","author":"Liu","year":"2015","journal-title":"Bioinformatics"},{"key":"2020080709362928700_ref25","first-page":"1","article-title":"Construction of drug network based on side effects and its application for drug repositioning","volume":"9","author":"Ye","year":"2014","journal-title":"PLoS One"},{"key":"2020080709362928700_ref26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.bjp.0707305","article-title":"In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling","volume":"152","author":"Ekins","year":"2007","journal-title":"Br J Pharmacol"},{"key":"2020080709362928700_ref27","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nrg.2016.87","article-title":"Network biology concepts in complex disease comorbidities","volume":"17","author":"Hu","year":"2016","journal-title":"Nat Rev Genet"},{"key":"2020080709362928700_ref28","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1093\/bib\/bbx017","article-title":"A review of network-based approaches to drug repositioning","volume":"19","author":"Lotfi Shahreza","year":"2018","journal-title":"Brief Bioinform"},{"key":"2020080709362928700_ref29","doi-asserted-by":"crossref","first-page":"2664","DOI":"10.1093\/bioinformatics\/btw228","article-title":"Drug repositioning based on comprehensive similarity measures and bi-random walk algorithm","volume":"32","author":"Luo","year":"2016","journal-title":"Bioinformatics"},{"key":"2020080709362928700_ref30","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.1038\/psp.2014.44","article-title":"Systematic analysis of new drug indications by drug\u2013gene\u2013disease coherent subnetworks","volume":"3","author":"Wang","year":"2014","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"2020080709362928700_ref31","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/clpt.2013.176","article-title":"Network-based approaches in drug discovery and early development","volume":"94","author":"Harrold","year":"2013","journal-title":"Clin Pharmacol Ther"},{"key":"2020080709362928700_ref32","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.2147\/OTT.S114318","article-title":"MicroRNA-216a promotes the metastasis and epithelial\u2013mesenchymal transition of ovarian cancer by suppressing the PTEN\/AKT pathway","volume":"10","author":"Liu","year":"2017","journal-title":"Onco Targets Ther"},{"key":"2020080709362928700_ref33","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nature09783","article-title":"Pervasive roles of microRNAs in cardiovascular biology","volume":"469","author":"Small","year":"2011","journal-title":"Nature"},{"key":"2020080709362928700_ref34","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1476-4598-8-102","article-title":"MicroRNAs in colorectal cancer: translation of molecular biology into clinical application","volume":"8","author":"Slaby","year":"2009","journal-title":"Mol Cancer"},{"key":"2020080709362928700_ref35","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/nature09284","article-title":"OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma","volume":"467","author":"Medina","year":"2010","journal-title":"Nature"},{"key":"2020080709362928700_ref36","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.3390\/ph6101195","article-title":"MicroRNAs as molecular targets for cancer therapy: on the modulation of microRNA expression","volume":"6","author":"Costa","year":"2013","journal-title":"Pharmaceuticals (Basel)"},{"key":"2020080709362928700_ref37","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1021\/cb300650y","article-title":"A molecular-beacon-based screen for small molecule inhibitors of miRNA maturation","volume":"8","author":"Bose","year":"2013","journal-title":"ACS Chem Biol"},{"key":"2020080709362928700_ref38","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/nrd3179","article-title":"Targeting microRNAs in cancer: rationale, strategies and challenges","volume":"9","author":"Garzon","year":"2010","journal-title":"Nat Rev Drug Discov"},{"key":"2020080709362928700_ref39","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.addr.2014.09.002","article-title":"Small molecule compounds targeting miRNAs for cancer therapy","volume":"81","author":"Monroig Pdel","year":"2015","journal-title":"Adv Drug Deliv Rev"},{"key":"2020080709362928700_ref40","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1021\/cb400668h","article-title":"Targeting the production of oncogenic microRNAs with multimodal synthetic small molecules","volume":"9","author":"Vo","year":"2014","journal-title":"ACS Chem Biol"},{"key":"2020080709362928700_ref41","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/srep00282","article-title":"Identification of links between small molecules and miRNAs in human cancers based on transcriptional responses","volume":"2","author":"Jiang","year":"2012","journal-title":"Sci Rep"},{"key":"2020080709362928700_ref42","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1093\/bioinformatics\/bts698","article-title":"SM2miR: a database of the experimentally validated small molecules' effects on microRNA expression","volume":"29","author":"Liu","year":"2013","journal-title":"Bioinformatics"},{"key":"2020080709362928700_ref43","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/bib\/bbs082","article-title":"Pharmaco-miR: linking microRNAs and drug effects","volume":"15","author":"Rukov","year":"2014","journal-title":"Brief Bioinform"},{"key":"2020080709362928700_ref44","doi-asserted-by":"crossref","DOI":"10.1098\/rsif.2013.1057","article-title":"Constructing and characterizing a bioactive small molecule and microRNA association network for Alzheimer's disease","volume":"11","author":"Meng","year":"2014","journal-title":"J R Soc Interface"},{"key":"2020080709362928700_ref45","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1039\/c2mb25298h","article-title":"Estrogen and retinoic acid antagonistically regulate several microRNA genes to control aerobic glycolysis in breast cancer cells","volume":"8","author":"Saumet","year":"2012","journal-title":"Mol Biosyst"},{"key":"2020080709362928700_ref46","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.3109\/10428194.2011.601476","article-title":"miR-15a\/16-1 enhances retinoic acid-mediated differentiation of leukemic cells and is up-regulated by retinoic acid","volume":"52","author":"Gao","year":"2011","journal-title":"Leuk Lymphoma"},{"key":"2020080709362928700_ref47","doi-asserted-by":"crossref","first-page":"E2620","DOI":"10.1210\/jc.2014-1883","article-title":"Integrative analysis of mRNA and miRNA array data reveals the suppression of retinoic acid pathway in regulatory T cells of Graves' disease","volume":"99","author":"Wang","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"2020080709362928700_ref48","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/jnc.12820","article-title":"MicroRNA-302b-inhibited E2F3 transcription factor is related to all trans retinoic acid-induced glioma cell apoptosis","volume":"131","author":"Chen","year":"2014","journal-title":"J Neurochem"},{"key":"2020080709362928700_ref49","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1471-2105-4-2","article-title":"An automated method for finding molecular complexes in large protein interaction networks","volume":"4","author":"Bader","year":"2003","journal-title":"BMC Bioinformatics"},{"key":"2020080709362928700_ref50","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jnutbio.2007.05.008","article-title":"[6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells","volume":"19","author":"Lee","year":"2008","journal-title":"J Nutr Biochem"},{"key":"2020080709362928700_ref51","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.bcp.2006.08.016","article-title":"Pharmacological profiling of disulfiram using human tumor cell lines and human tumor cells from patients","volume":"73","author":"Wickstr\u00f6m","year":"2007","journal-title":"Biochem Pharmacol"},{"key":"2020080709362928700_ref52","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.cbi.2010.06.007","article-title":"Combinatorial effect of fish oil (Maxepa) and 1alpha,25-dihydroxyvitamin D(3) in the chemoprevention of DMBA-induced mammary carcinogenesis in rats","volume":"188","author":"Chatterjee","year":"2010","journal-title":"Chem Biol Interact"},{"key":"2020080709362928700_ref53","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3816\/CBC.2010.n.005","article-title":"Pathologic complete response to preoperative sequential doxorubicin\/cyclophosphamide and single-agent taxane with or without trastuzumab in stage II\/III HER2-positive breast cancer","volume":"10","author":"Chumsri","year":"2010","journal-title":"Clin Breast Cancer"},{"key":"2020080709362928700_ref54","doi-asserted-by":"crossref","first-page":"773","DOI":"10.3892\/ijmm_00000291","article-title":"Experimental study of the anti-cancer mechanism of tanshinone IIA against human breast cancer","volume":"24","author":"Lu","year":"2009","journal-title":"Int J Mol Med"},{"key":"2020080709362928700_ref55","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.jsbmb.2010.06.004","article-title":"COX-2 inhibitor nimesulide analogs are aromatase suppressors in breast cancer cells","volume":"122","author":"Su","year":"2010","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020080709362928700_ref56","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1023\/A:1008252128623","article-title":"Ataxia following docetaxel infusion","volume":"8","author":"Hofstra","year":"1997","journal-title":"Ann Oncol"},{"key":"2020080709362928700_ref57","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/sj.bjc.6600780","article-title":"Phase I\/II study of gemcitabine plus mitoxantrone as salvage chemotherapy in metastatic breast cancer","volume":"88","author":"Lorusso","year":"2003","journal-title":"Br J Cancer"},{"key":"2020080709362928700_ref58","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/j.1349-7006.2001.tb01154.x","article-title":"Preventive effects of isoflavones, genistein and daidzein, on estradiol-17beta-related endometrial carcinogenesis in mice","volume":"92","author":"Lian","year":"2001","journal-title":"Jpn J Cancer Res"},{"key":"2020080709362928700_ref59","doi-asserted-by":"crossref","first-page":"D972","DOI":"10.1093\/nar\/gkw838","article-title":"The Comparative Toxicogenomics Database: update 2017","volume":"45","author":"Davis","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2020080709362928700_ref60","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s12035-013-8484-9","article-title":"Targeting estrogen receptors for the treatment of Alzheimer's disease","volume":"49","author":"Lee","year":"2014","journal-title":"Mol Neurobiol"},{"key":"2020080709362928700_ref61","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.1093\/nar\/gkp500","article-title":"Estradiol-regulated microRNAs control estradiol response in breast cancer cells","volume":"37","author":"Bhat-Nakshatri","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2020080709362928700_ref62","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1093\/nar\/gkp117","article-title":"Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells","volume":"37","author":"Wickramasinghe","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2020080709362928700_ref63","doi-asserted-by":"crossref","DOI":"10.3390\/genes9040174","article-title":"The role of microRNAs in Alzheimer's disease and their therapeutic potentials","volume":"9","author":"Miya Shaik","year":"2018","journal-title":"Genes (Basel)"},{"key":"2020080709362928700_ref64","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.neulet.2016.05.049","article-title":"Regulation of proapoptotic proteins Bak1 and p53 by miR-125b in an experimental model of Alzheimer's disease: protective role of 17beta-estradiol","volume":"629","author":"Micheli","year":"2016","journal-title":"Neurosci Lett"},{"key":"2020080709362928700_ref65","doi-asserted-by":"crossref","first-page":"D1100","DOI":"10.1093\/nar\/gkr777","article-title":"ChEMBL: a large-scale bioactivity database for drug discovery","volume":"40","author":"Gaulton","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2020080709362928700_ref66","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13321-018-0303-x","article-title":"A new chemoinformatics approach with improved strategies for effective predictions of potential drugs","volume":"10","author":"Hao","year":"2018","journal-title":"J Cheminform"},{"key":"2020080709362928700_ref67","article-title":"Open-source chemogenomic data-driven algorithms for predicting drug\u2013target interactions","author":"Hao","year":"2018","journal-title":"Brief Bioinform"},{"key":"2020080709362928700_ref68","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.3389\/fimmu.2018.01357","article-title":"Arsenic trioxide enhances the NK cell cytotoxicity against acute promyelocytic leukemia while simultaneously inhibiting its bio-genesis","volume":"9","author":"Alex","year":"2018","journal-title":"Front Immunol"},{"key":"2020080709362928700_ref69","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1007\/s00775-018-1595-z","article-title":"Low dosage of arsenic trioxide (As2O3) inhibits angiogenesis in epithelial ovarian cancer without cell apoptosis","volume":"23","author":"Luo","year":"2018","journal-title":"J Biol Inorg Chem"},{"key":"2020080709362928700_ref70","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.lfs.2018.05.006","article-title":"Arsenic trioxide induces apoptosis and inhibits the growth of human liver cancer cells","volume":"205","author":"Sadaf","year":"2018","journal-title":"Life Sci"},{"key":"2020080709362928700_ref71","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/leu.2016.311","article-title":"Arsenic trioxide degrades NPM-ALK fusion protein and inhibits growth of ALK-positive anaplastic large cell lymphoma","volume":"31","author":"Piao","year":"2017","journal-title":"Leukemia"},{"key":"2020080709362928700_ref72","doi-asserted-by":"crossref","first-page":"5898","DOI":"10.1073\/pnas.1523975113","article-title":"Design of a small molecule against an oncogenic noncoding RNA","volume":"113","author":"Velagapudi","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020080709362928700_ref73","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.brainres.2016.05.011","article-title":"Geniposide reduces \u03b1-synuclein by blocking microRNA-21\/lysosome-associated membrane protein 2A interaction in Parkinson disease models","volume":"1644","author":"Su","year":"2016","journal-title":"Brain Res"},{"key":"2020080709362928700_ref74","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nature13073","article-title":"Inhibition of miR-25 improves cardiac contractility in the failing heart","volume":"508","author":"Wahlquist","year":"2014","journal-title":"Nature"},{"key":"2020080709362928700_ref75","doi-asserted-by":"crossref","first-page":"D1070","DOI":"10.1093\/nar\/gkt1023","article-title":"HMDD v2.0: a database for experimentally supported human microRNA and disease associations","volume":"42","author":"Li","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2020080709362928700_ref76","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3322\/caac.21338","article-title":"Cancer statistics in China, 2015","volume":"66","author":"Chen","year":"2016","journal-title":"CA Cancer J Clin"},{"key":"2020080709362928700_ref77","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.ccm.2011.08.005","article-title":"Pathology of lung cancer","volume":"32","author":"Travis","year":"2011","journal-title":"Clin Chest Med"},{"key":"2020080709362928700_ref78","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1002\/1097-0142(19870915)60:6<1190::AID-CNCR2820600606>3.0.CO;2-7","article-title":"5-Fluorouracil, doxorubicin, and mitomycin-C in the treatment of adenocarcinoma and large cell carcinoma of the lung","volume":"60","author":"Shaw","year":"1987","journal-title":"Cancer"},{"key":"2020080709362928700_ref79","doi-asserted-by":"crossref","first-page":"5068","DOI":"10.1158\/0008-5472.CAN-17-0567","article-title":"Gemcitabine and Chk1 inhibitor AZD7762 synergistically suppress the growth of Lkb1-deficient lung adenocarcinoma","volume":"77","author":"Liu","year":"2017","journal-title":"Cancer Res"},{"key":"2020080709362928700_ref80","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1039\/c3an00975k","article-title":"Raman micro spectroscopy study of the interaction of vincristine with A549 cells supported by expression analysis of bcl-2 protein","volume":"138","author":"Nawaz","year":"2013","journal-title":"Analyst"},{"key":"2020080709362928700_ref81","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/annonc\/mdv573","article-title":"Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort","volume":"27","author":"Mazi\u00e8res","year":"2016","journal-title":"Ann Oncol"},{"key":"2020080709362928700_ref82","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.phymed.2012.03.005","article-title":"Curcumin reverses cis-platin resistance and promotes human lung adenocarcinoma A549\/DDP cell apoptosis through HIF-1\u03b1 and caspase-3 mechanisms","volume":"19","author":"Ye","year":"2012","journal-title":"Phytomedicine"},{"key":"2020080709362928700_ref83","doi-asserted-by":"crossref","first-page":"16481","DOI":"10.1038\/s41598-017-16745-z","article-title":"All-trans retinoic acid enhances cytotoxicity of CIK cells against human lung adenocarcinoma by upregulating MICA and IL-2 secretion","volume":"7","author":"Fan","year":"2017","journal-title":"Sci Rep"},{"key":"2020080709362928700_ref84","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jinorgbio.2017.07.016","article-title":"Impact of the Cu(II) ions on the chemical and biological properties of goserelin\u2014coordination pattern, DNA degradation, oxidative reactivity and in vitro cytotoxicity","volume":"175","author":"Walencik","year":"2017","journal-title":"J Inorg Biochem"},{"key":"2020080709362928700_ref85","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.3892\/ijo.2013.2120","article-title":"Effect of metformin on residual cells after chemotherapy in a human lung adenocarcinoma cell line","volume":"43","author":"Kitazono","year":"2013","journal-title":"Int J Oncol"},{"key":"2020080709362928700_ref86","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.3892\/or_00000975","article-title":"Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186* signaling pathway","volume":"24","author":"Zhang","year":"2010","journal-title":"Oncol Rep"},{"key":"2020080709362928700_ref87","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.3892\/or.2015.4258","article-title":"Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K\/Akt signaling pathway","volume":"34","author":"Jin","year":"2015","journal-title":"Oncol Rep"},{"key":"2020080709362928700_ref88","doi-asserted-by":"crossref","first-page":"32805","DOI":"10.18632\/oncotarget.5352","article-title":"MiR-200b regulates autophagy associated with chemoresistance in human lung adenocarcinoma","volume":"6","author":"Pan","year":"2015","journal-title":"Oncotarget"},{"key":"2020080709362928700_ref89","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1093\/bioinformatics\/btv417","article-title":"Identifying novel associations between small molecules and miRNAs based on integrated molecular networks","volume":"31","author":"Lv","year":"2015","journal-title":"Bioinformatics"},{"key":"2020080709362928700_ref90","doi-asserted-by":"crossref","first-page":"W623","DOI":"10.1093\/nar\/gkp456","article-title":"PubChem: a public information system for analyzing bioactivities of small molecules","volume":"37","author":"Wang","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2020080709362928700_ref91","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/bioinformatics\/btm554","article-title":"Computing topological parameters of biological networks","volume":"24","author":"Assenov","year":"2008","journal-title":"Bioinformatics"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/21\/2\/498\/33585674\/bbz012.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/21\/2\/498\/33585674\/bbz012.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T22:18:02Z","timestamp":1694557082000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/21\/2\/498\/5306502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,11]]},"references-count":91,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2,11]]},"published-print":{"date-parts":[[2020,3,23]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbz012","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,3]]},"published":{"date-parts":[[2019,2,11]]}}}