C63
MicroRNAs in childhood rhabdomyosarcoma
Edoardo Missiaglia, Chris Shepherd, Sheena Patel, Janet Shipley
The Institute of Cancer Research, Sutton, UK
Background
Rhabdomyosarcomas are soft tissue sarcomas resembling myogenic development and are one of the leading causes of paediatric cancer death.
MicroRNAs (miRNA) are recently discovered short RNA molecules that play a key role in the regulation of gene expression. Expression of miRNAs in various tumour types correlates with patient outcome and differentiation status and have demonstrable tumour suppressor and oncogenic roles. Interestingly, some miRNAs have been involved in myogenesis.
Method
Thirty six primary rhabdomyosarcoma (RMS) tumours, 18 RMS cell lines, 7 normal muscle samples and 2 myoblasts were screened for miRNA expression using a microarray platform containing 359 human probes. Quantitative RT-PCR based assay was employed to validate our findings. The functional role of selected miRNA differentially expressed between RMS and normal muscle was then evaluated by artificially modulating their expression in RMS cell lines.
Results
The analysis has identified 40 and 31 miRNAs over and under expressed compared to normal muscle, respectively; five of them have been confirmed by other means in a larger set of samples. A number of the identified miRNAs have been associated with muscle differentiation and tumourigenesis, whilst others are novel. Functional studies have confirmed the involvement of selected miRNAs in RMS tumourigenesis. In addition, the expression of some miRNAs was associated with overall patient survival.
Conclusion
The analysis identified several miRNAs potentially involved in rhabdomyosarcoma development as well as associated with poorer outcome. Further studies will elucidate their biological role and their potential as therapeutic targets in rhabdomyosarcomas.
