title: Construction of therapeutically relevant human prostate epithelial fate map by utilising miRNA and mRNA microarray expression data.
abstract: BACKGROUND
  Objective identification of key miRNAs from transcriptomic data is difficult owing to the inherent inconsistencies within miRNA target-prediction algorithms and the promiscuous nature of miRNA-mRNA target relationship.
  
  
  METHODS
  An integrated database of miRNAs and their 'relevant' mRNA targets was generated from validated miRNA and mRNA microarray data sets generated from patient-derived prostate epithelial normal and cancer stem-like cells (SCs) and committed basal (CB) cells. The effect of miR-542-5p inhibition was studied to provide proof-of-principle for database utility.
  
  
  RESULTS
  Integration of miRNA-mRNA databases showed that signalling pathways and processes can be regulated by a single or relatively few miRNAs, for example, DNA repair/Notch pathway by miR-542-5p, P=0.008. Inhibition of miR-542-5p in CB cells (thereby achieving miR-542-5p expression levels similar to SCs) promoted efficient DNA repair and activated expression of Notch reporters, HES1 and Survivin, without inducing dedifferentiation into SCs.
  
  
  CONCLUSIONS
  Our novel framework impartially identifies therapeutically relevant miRNA candidates from transcriptomic data sets.
authors.affiliation: Department of Biology, YCR Cancer Research Unit, University of York, York YO10 5DD, North Yorkshire, UK.
authors.forename: Jayant K
authors.initials: JK
authors.lastname: Rane
authors.affiliation: 1] Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere and Tampere University Hospital, Biokatu 8, Tampere 33520, Finland [2] Department of Signal Processing, Tampere University of Technology, Korkeakoulunkatu 10, Tampere 33720, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Ylipää
authors.affiliation: Department of Biology, YCR Cancer Research Unit, University of York, York YO10 5DD, North Yorkshire, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Adamson
authors.affiliation: 1] Hull York Medical School, University of Hull, Hull HU6 7RX, East Yorkshire, UK [2] Department of Urology, Castle Hill Hospital, Cottingham HU16 5JQ, East Yorkshire, UK.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Mann
authors.affiliation: 1] Hull York Medical School, University of Hull, Hull HU6 7RX, East Yorkshire, UK [2] Department of Urology, Castle Hill Hospital, Cottingham HU16 5JQ, East Yorkshire, UK.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Simms
authors.affiliation: Department of Biology, YCR Cancer Research Unit, University of York, York YO10 5DD, North Yorkshire, UK.
authors.forename: Anne T
authors.initials: AT
authors.lastname: Collins
authors.affiliation: Molecular Biology of Prostate Cancer Group, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere and Tampere University Hospital, BioMediTech, Biokatu 8, Tampere 33520, Finland.
authors.forename: Tapio
authors.initials: T
authors.lastname: Visakorpi
authors.affiliation: 1] Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere and Tampere University Hospital, Biokatu 8, Tampere 33520, Finland [2] Department of Signal Processing, Tampere University of Technology, Korkeakoulunkatu 10, Tampere 33720, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Nykter
authors.affiliation: 1] Department of Biology, YCR Cancer Research Unit, University of York, York YO10 5DD, North Yorkshire, UK [2] Department of Urology, Castle Hill Hospital, Cottingham HU16 5JQ, East Yorkshire, UK.
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Maitland
mesh_terms: D004260:DNA Repair / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics*; D051880:Receptors, Notch / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D051880:Receptors, Notch