Oztemur, Y.Bekmez, T.Aydos, A.Yulug I.G.Bozkurt, B.Dedeoglu, B.G.2016-02-082016-02-08201519326203http://hdl.handle.net/11693/21948Breast cancer is one of the most important causes of cancer-related deaths worldwide in women. In addition to gene expression studies, the progressing work in the miRNA area including miRNA microarray studies, brings new aspects to the research on the cancer development and progression. Microarray technology has been widely used to find new biomarkers in research and many transcriptomic microarray studies are available in public databases. In this study, the breast cancer miRNA and mRNA microarray studies were collected according to the availability of their data and clinical information, and combined by a newly developed ranking-based meta-analysis approach to find out candidate miRNA biomarkers (meta-miRNAs) that classify breast cancers according to their grades and explain the relation between miRNAs and mRNAs. This approach provided meta-miRNAs specific to breast cancer grades, pointing out let-7 family members as grade classifiers. The qRTPCR studies performed with independent breast tumors confirmed the potential biomarker role of let-7 family members (meta-miRNAs). The concordance between the meta-mRNAs and miRNA target genes specific to tumor grade (common genes) supported the idea of mRNAs as miRNA targets. The pathway analysis results showed that most of the let-7 family miRNA targets, and also common genes, were significantly taking part in cancer-related pathways. The qRT-PCR studies, together with bioinformatic analyses, confirmed the results of meta-analysis approach, which is dynamic and allows combining datasets from different platforms. © 2015 Oztemur et al.EnglishB lymphocyte induced maturation protein 1biological markerdendritic cell lysosome associated membrane proteinheme oxygenase 1mammalian target of rapamycinmessenger RNAmicroRNAmicroRNA 30a 3pmicroRNA 30a 5pmicroRNA 320microRNA 7microRNA 99amicroRNA let 7microRNA let 7amicroRNA let 7bmicroRNA let 7cmicroRNA let 7dmicroRNA let 7emicroRNA let 7fmicroRNA let 7gmicroRNA let 7iminichromosome maintenance protein 2mitogen activated protein kinasemonocarboxylate transporter 4suppressor of cytokine signaling 1thioredoxin reductase 1transforming growth factor betaunclassified drugvasculotropinapoptosisArticlebreast cancercancer gradingcell cycledown regulationgenegene expression regulationgenetic associationHMOX1 genehumanhuman tissueIQGAP3 geneLAMP3 geneLMNB2 geneMCM2 geneME1 genePOLA2 genePOLR2C genePRDM1 genePSAT1 geneRDH10 genereverse transcription polymerase chain reactionSAMSN1 geneSEC24A geneSELL genesignal transductionSLC16A3 geneSLC25A13 geneSLC7A5 geneSOAT1 geneSOCS1 geneSQSTM1 geneSRM geneSTMN1 geneTCF19 geneTRIP13 geneTXNRD1 geneTYMS geneupregulationArticle10.1371/journal.pone.0126837