Abstract

Functional evaluation for the utilisation of recognised oncogenic miRNAs as neuroblastoma chemoresistance biomarkers

Duncan Ayers, Postgraduate Researcher, University of Malta / University of Manchester

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 re! sistant tumours (1). The purpose of this study is to functionally evaluate known oncogenic miRNAs that may have direct effect on neuroblastoma (NB) drug resistance. METHODS: Individual subcultures of chemosensitive SH-SY5Y and NGP cells were rendered chemoresistant to doxorubicin or etoposide over a period of 18 months. In each validated chemoresistance model, miR-21, miR-25 and miR-221 antagonists are transiently transfected within the chemoresistant subculture (individually / in combination), followed by a cell-based assay for identifying modulation of chemoresistance phenotype. All miRNAs were selected from previous scientific literature and/or based on previous research involving high-throughput miRNA expression profiling screens (2,3). RESULTS: Experimental phase is currently in progress. CONCLUSIONS: This study potentially elucidates three novel chemoresistance miRNA biomarkers in four separate chemoresistant NB cell line models, spanning two cell lines (SH-SY5Y & NGP) and two chemotherapeutic agents (doxorubicin & etoposide). 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.