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MicroRNA-206 expression levels correlate with clinical behaviour of rhabdomyosarcomas
E Missiaglia1, C J Shepherd, S Patel
1Molecular Cytogenetics Team, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Background:
Rhabdomyosarcomas (RMSs) are primarily paediatric sarcomas that resemble developing skeletal muscle. Our aim was to determine the effects of microRNAs (miRNA) that have been implicated in muscle development on the clinical behaviour of RMSs.
Methods:
Expression levels of miR-1, miR-206, miR-133a and miR-133b were quantified by RT-PCR in 163 primary paediatric RMSs, plus control tissues, and correlated with clinico-pathological features. Correlations with parallel gene expression profiling data for 84 samples were used to identify pathways associated with miR-206. Synthetic miR-206 was transfected into RMS cell lines and phenotypic responses assessed.
Results:
Muscle-specific miRNAs levels were lower in RMSs compared with skeletal muscle but generally higher than in other normal tissues. Low miR-206 expression correlated with poor overall survival and was an independent predictor of shorter survival in metastatic embryonal and alveolar cases without PAX3/7-FOXO1 fusion genes. Low miR-206 expression also significantly correlated with high SIOP stage and the presence of metastases at diagnosis. High miR-206 expression strongly correlated with genes linked to muscle differentiation and low expression was associated with genes linked to MAPkinase and NFKappaB pathway activation. Increasing miR-206 expression in cell lines inhibited cell growth and migration and induced apoptosis that was associated with myogenic differentiation in some, but not all, cell lines.
Conclusion:
miR-206 contributes to the clinical behaviour of RMSs and the pleiotropic effects of miR-206 supports therapeutic potential.
Insights
MicroRNA-206 (miR-206) levels impact rhabdomyosarcoma (RMS) behavior. Low miR-206 predicts poorer survival in pediatric RMS, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Rhabdomyosarcomas (RMSs) are pediatric sarcomas resembling developing skeletal muscle.
- MicroRNAs (miRNAs) play roles in muscle development and may influence RMS clinical behavior.
Purpose of the Study:
- To investigate the effect of muscle-specific miRNAs on the clinical behavior of pediatric RMS.
- To correlate miRNA expression with clinico-pathological features and molecular pathways in RMS.
Main Methods:
- Quantified miR-1, miR-206, miR-133a, and miR-133b expression in 163 RMS tissues using RT-PCR.
- Correlated miRNA levels with clinico-pathological data and gene expression profiles.
- Assessed phenotypic responses to miR-206 transfection in RMS cell lines.
Main Results:
- Muscle-specific miRNAs were generally lower in RMS compared to skeletal muscle.
- Low miR-206 expression correlated with poor survival, advanced stage, and metastasis in RMS.
- miR-206 influenced muscle differentiation pathways and affected RMS cell growth, migration, and apoptosis.
Conclusions:
- miR-206 plays a significant role in the clinical behavior of rhabdomyosarcomas.
- The pleiotropic effects of miR-206 suggest its potential as a therapeutic target in RMS.
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