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

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JournalBritish journal of cancer
DateE-pub ahead of print - 23 Jul 2015
DatePublished (current) - 23 Jul 2015
Early online date23/07/15
Original languageEnglish

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.British Journal of Cancer advance online publication 23 July 2015. doi:10.1038/bjc.2015.262 www.bjcancer.com.

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