MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas.
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Rhabdomyosarcomas (RMS) in children and adolescents are heterogeneous sarcomas broadly defined by skeletal muscle features and the presence/absence of PAX3/7-FOXO1 fusion genes. MicroRNAs are small non-coding RNAs that regulate gene expression in a cell context specific manner. Sequencing analyses of microRNAs in 64 RMS revealed expression patterns separating skeletal muscle, fusion gene positive and negative RMS. Integration with parallel gene expression data assigned biological functions to 12 co-expression networks/modules that reassuringly included myogenic roles strongly correlated with microRNAs known in myogenesis and RMS development. Modules also correlated with clinical outcome and fusion status. Regulation of microRNAs by the fusion protein was demonstrated after PAX3-FOXO1 reduction, exemplified by miR-9-5p. MiR-9-5p levels correlated with poor outcome, even within fusion gene positive RMS, and were higher in metastatic versus non-metastatic disease. MiR-9-5p reduction inhibited RMS cell migration. Our findings reveal microRNAs in a regulatory framework of biological and clinical significance in RMS.
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Cell Line, Tumor
Genetic Predisposition to Disease
Oncogene Proteins, Fusion
Reproducibility of Results
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Paired Box Transcription Factors
Gene Regulatory Networks
High-Throughput Nucleotide Sequencing
Sarcoma Molecular Pathology
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Cancer letters, 2017, 385 pp. 251 - 260