Construction of Therapeutically Relevant Human Prostate Epithelial Fate Map by Utilising miRNA and mRNA Microarray Expression Data

Br J Cancer. 2015 Aug 11;113(4):611-5. doi: 10.1038/bjc.2015.262. Epub 2015 Jul 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Repair / genetics
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Prostate / metabolism*
  • Prostate / pathology*
  • RNA, Messenger / genetics*
  • Receptors, Notch / genetics
  • Signal Transduction / genetics

Substances

  • MicroRNAs
  • RNA, Messenger
  • Receptors, Notch