title: Identification of miRNAs contributing to neuroblastoma chemoresistance.
abstract: BACKGROUND
  The emergence of the role of microRNAs (miRNAs) in exacerbating drug resistance of tumours is recently being highlighted as a crucial research field for future clinical management of drug resistant tumours. The purpose of this study was to identify dys-regulations in expression of individual and/or networks of miRNAs that may have direct effect on neuroblastoma (NB) drug resistance.
  
  
  METHODS
  Individual subcultures of chemosensitive SH-SY5Y and UKF-NB-3 cells were rendered chemoresistant to doxorubicin (SH-SY5Y, UKF-NB-3) or etoposide (SH-SY5Y). In each validated chemoresistance model, the parental and subcultured cell lines were analysed for miRNA expression profiling, using a high-throughput quantitative polymerase chain reaction (RT-qPCR) miRNA profiling platform for a total of 668 miRNAs.
  
  
  RESULTS
  A unique expression signature of miRNAs was found to be differentially expressed (higher than 2-fold change) within all three NB chemoresistance models. Four miRNAs were upregulated in the subcultured chemoresistant cell line. Three miRNAs were found to be downregulated in the chemoresistant cell lines for all models.
  
  
  CONCLUSIONS
  Based on the initial miRNA findings, this study elucidates the dys-regulation of four miRNAs in three separate NB chemoresistant cell line models, spanning two cell lines (SH-SY5Y and UKF-NB-3) and two chemotherapeutic agents (doxorubicin and etoposide). These miRNAs may thus be possibly linked to chemoresistance induction in NB. Such miRNAs are good candidates to be novel drug targets for future miRNA based therapies against aggressive tumours that are not responding to conventional chemotherapy.
authors.affiliation: Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta ; Manchester Institute of Biotechnology, Faculty of Medical and Human Sciences, The University of Manchester, United Kingdom.
authors.forename: Duncan
authors.initials: D
authors.lastname: Ayers
authors.affiliation: Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Mestdagh
authors.affiliation: Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Van Maerken
authors.affiliation: Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
keywords: Chemoresistance; Drug; Neuroblastoma; Resistance; miRNA