Construction of therapeutically relevant human prostate epithelial fate map by utilising miRNA and mRNA microarray expression data

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.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.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.Our novel framework impartially identifies therapeutically relevant miRNA candidates from transcriptomic data sets.