MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas.
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Date
2017-01-28Author
Missiaglia, E
Shepherd, CJ
Aladowicz, E
Olmos, D
Selfe, J
Pierron, G
Delattre, O
Walters, Z
Shipley, J
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
Cell Line, Tumor
Humans
Rhabdomyosarcoma, Alveolar
Rhabdomyosarcoma, Embryonal
Neoplasm Invasiveness
Genetic Predisposition to Disease
Oncogene Proteins, Fusion
MicroRNAs
Reproducibility of Results
Gene Fusion
Gene Expression Profiling
Transfection
Computational Biology
Cell Movement
Gene Expression Regulation, Neoplastic
Phenotype
Databases, Genetic
Paired Box Transcription Factors
Gene Regulatory Networks
High-Throughput Nucleotide Sequencing
Biomarkers, Tumor
Research team
Sarcoma Molecular Pathology
Language
eng
Date accepted
2016-10-03
License start date
2017-01
Citation
Cancer letters, 2017, 385 pp. 251 - 260
Publisher
ELSEVIER IRELAND LTD