MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas
MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas
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.
Biomarkers, Tumor, Cell Line, Tumor, Cell Movement, Computational Biology, Databases, Genetic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Fusion, Gene Regulatory Networks, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, MicroRNAs, Neoplasm Invasiveness, Oncogene Proteins, Fusion, Paired Box Transcription Factors, Phenotype, Reproducibility of Results, Rhabdomyosarcoma, Alveolar, Rhabdomyosarcoma, Embryonal, Transfection, Journal Article, Research Support, Non-U.S. Gov't
251-260
Missiaglia, Edoardo
5c63d29e-3aad-4bc0-82ec-aa7d18896207
Shepherd, Chris J
6f2f634a-fe6e-4e04-81d9-2a197c51729e
Aladowicz, Ewa
ae5a9dec-fc44-4229-8fd8-87b457967635
Olmos, David
ed104cad-6f27-4f4d-9572-941f61cdb85f
Selfe, Joanna
3853ed08-1f71-4983-a49f-3dba1625383f
Pierron, Gaëlle
63585a5f-f66e-4d7a-88f1-c79174586c5c
Delattre, Olivier
ab10aa37-2ad3-4712-b371-685f820e6eb2
Walters, Zoe
e1ccd35d-63a9-4951-a5da-59122193740d
Shipley, Janet
c4bd3760-d826-42ba-8321-ce78582034ac
28 January 2017
Missiaglia, Edoardo
5c63d29e-3aad-4bc0-82ec-aa7d18896207
Shepherd, Chris J
6f2f634a-fe6e-4e04-81d9-2a197c51729e
Aladowicz, Ewa
ae5a9dec-fc44-4229-8fd8-87b457967635
Olmos, David
ed104cad-6f27-4f4d-9572-941f61cdb85f
Selfe, Joanna
3853ed08-1f71-4983-a49f-3dba1625383f
Pierron, Gaëlle
63585a5f-f66e-4d7a-88f1-c79174586c5c
Delattre, Olivier
ab10aa37-2ad3-4712-b371-685f820e6eb2
Walters, Zoe
e1ccd35d-63a9-4951-a5da-59122193740d
Shipley, Janet
c4bd3760-d826-42ba-8321-ce78582034ac
Missiaglia, Edoardo, Shepherd, Chris J, Aladowicz, Ewa, Olmos, David, Selfe, Joanna, Pierron, Gaëlle, Delattre, Olivier, Walters, Zoe and Shipley, Janet
(2017)
MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas.
Cancer Letters, 385, .
(doi:10.1016/j.canlet.2016.10.011).
Abstract
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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More information
Accepted/In Press date: 3 October 2016
e-pub ahead of print date: 29 October 2016
Published date: 28 January 2017
Keywords:
Biomarkers, Tumor, Cell Line, Tumor, Cell Movement, Computational Biology, Databases, Genetic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Fusion, Gene Regulatory Networks, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, MicroRNAs, Neoplasm Invasiveness, Oncogene Proteins, Fusion, Paired Box Transcription Factors, Phenotype, Reproducibility of Results, Rhabdomyosarcoma, Alveolar, Rhabdomyosarcoma, Embryonal, Transfection, Journal Article, Research Support, Non-U.S. Gov't
Identifiers
Local EPrints ID: 416326
URI: http://eprints.soton.ac.uk/id/eprint/416326
ISSN: 0304-3835
PURE UUID: 400449f7-1b2c-421e-a0e3-1cc63bcb07aa
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Date deposited: 13 Dec 2017 17:30
Last modified: 16 Mar 2024 04:32
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Author:
Edoardo Missiaglia
Author:
Chris J Shepherd
Author:
Ewa Aladowicz
Author:
David Olmos
Author:
Joanna Selfe
Author:
Gaëlle Pierron
Author:
Olivier Delattre
Author:
Janet Shipley
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