MicroRNA expression and its clinical implications in Ewing's sarcoma

Ewing's sarcoma (EWS) is the second most common primary bone cancer, and is a predominant childhood malignant disease. Due to limited understanding of its pathogenesis and frequent occurrence of resistance to conventional types of treatment, its management remains difficult, and mortality is frequent. Development of EWS is a multistep process involving genetic and epigenetic alterations of protein-coding proto-oncogenes and tumour-suppressor genes. MicroRNAs (miRNAs) have recently been discovered as a new category of non-protein coding; small RNA molecules that regulate gene expression at the post-transcriptional level. Substantial numbers of deregulated miRNAs have been documented in EWS and their biological significance has been confirmed in multiple functional experiments. Several studies have confirmed involvement of miRNAs in various steps of EWS pathogenesis, from occurrence to metastasis. Functionally, miRNA dysregulation may promote cell-cycle progression, confer resistance to apoptosis, and enhance invasiveness and metastasis. These miRNAs have opened a novel field in cancer research with potential clinical utilization for screening, diagnosis, prognostics and prediction of response to treatment. Elucidating biological aspects of miRNA dysregulation may help better understand pathogenesis of EWS and promote development of miRNA directed-therapeutics against it.