O-089 Micrornas And Chemoresistance In Neuroblastoma

Abstract

Background Neuroblastoma is a neoplasm of the sympathetic nervous system representing the most frequently diagnosed solid tumour in infants. Despite continued improvements in cancer treatment, the overall survival of patients with high risk neuroblastoma is still only 40–50%. Irrespective of risk factors, neuroblastomas generally respond well to initial therapy. However, the majority of high risk patients relapse with tumours refractory to standard chemotherapeutic agents. Therefore, the understanding of biological and molecular aspects of drug resistance in neuroblastoma may provide new opportunities for therapy of aggressive neuroblastoma. Recent evidence has revealed a substantial role of microRNAs (miRNAs) in multidrug resistance in various cancer types. MicroRNAs are small (18–24 nucleotides) non-coding RNA molecules that regulate the expression of genes at the post-transcriptional level by either direct cleavage of target mRNAs or repression of translation. Several studies indicate that deviant expression of certain miRNAs correlate with poor clinical outcome in neuroblastoma. However, the role of miRNAs in neuroblastoma cell resistance to chemotherapeutic drugs is poorly understood. Methods To explore the role of miRNAs in the resistance of neuroblastoma cells to anticancer drugs, we generated miRNA cDNA libraries from six isogenic human neuroblastoma cell line pairs established from the same patients at the time of initial diagnosis and relapse following therapy. To analyse expression patterns of miRNAs, a deep sequencing analysis (SOLiD sequencing) was performed using the miRNA cDNA libraries. Results Deep sequencing analysis (SOLiD sequencing) revealed differential expression patterns of miRNAs before and after treatment. Systematic analysis of these miRNA expression patterns identified potential alterations in pathways associated with drug resistance suggesting that dysregulation of miRNAs might influence sensitivity to therapy. Conclusion We anticipate that our findings will provide new insights into the molecular mechanisms of drug resistance in neuroblastoma.