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

Research output: Contribution to journalArticleScientificpeer-review

Details

Original languageEnglish
Pages (from-to)611-615
Number of pages5
JournalBritish Journal of Cancer
Volume113
Issue number4
DOIs
Publication statusPublished - 11 Aug 2015
Publication typeA1 Journal article-refereed

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.

ASJC Scopus subject areas

Keywords

  • cancer stem cell, DNA repair, epithelial hierarchy, miRNA-mRNA integration, Notch pathway, prostate cancer

Publication forum classification

Field of science, Statistics Finland