Glioma microvesicles carry selectively packaged coding and noncoding RNAs which alter gene expression in recipient cells

Li, CCY; Eaton, SA; Young, PE; Lee, M; Shuttleworth, R; Humphreys, DT; Grau, GE; Combes, V; Bebawy, M; Gong, J; Brammah, S; Buckland, ME; Suter, CM

Glioma microvesicles carry selectively packaged coding and noncoding RNAs which alter gene expression in recipient cells

Li, CCY Eaton, SA Young, PE Lee, M Shuttleworth, R Humphreys, DT Grau, GE Combes, V

Bebawy, M

Gong, J Brammah, S Buckland, ME Suter, CM

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Publication Type:: Journal Article
Citation:: RNA Biology, 2013, 10 (8), pp. 1333 - 1344
Issue Date:: 2013-01-01

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Field	Value	Language
dc.contributor.author	Li, CCY	en_US
dc.contributor.author	Eaton, SA	en_US
dc.contributor.author	Young, PE	en_US
dc.contributor.author	Lee, M	en_US
dc.contributor.author	Shuttleworth, R	en_US
dc.contributor.author	Humphreys, DT	en_US
dc.contributor.author	Grau, GE	en_US
dc.contributor.author	Combes, V https://orcid.org/0000-0003-2178-3596	en_US
dc.contributor.author	Bebawy, M https://orcid.org/0000-0003-2606-921X	en_US
dc.contributor.author	Gong, J	en_US
dc.contributor.author	Brammah, S	en_US
dc.contributor.author	Buckland, ME	en_US
dc.contributor.author	Suter, CM	en_US
dc.date.issued	2013-01-01	en_US
dc.identifier.citation	RNA Biology, 2013, 10 (8), pp. 1333 - 1344	en_US
dc.identifier.issn	1547-6286	en_US
dc.identifier.uri	http://hdl.handle.net/10453/36917
dc.identifier.uri	http://hdl.handle.net/10453/23658
dc.description.abstract	Interactions between glioma cells and their local environment are critical determinants of brain tumor growth, infiltration and neovascularisation. Communication with host cells and stroma via microvesicles represents one pathway by which tumors can modify their surroundings to achieve a tumor-permissive environment. Here we have taken an unbiased approach to identifying RNAs in glioma-derived microvesicles, and explored their potential to regulate gene expression in recipient cells. We find that glioma microvesicles are predominantly of exosomal origin and contain complex populations of coding and noncoding RNAs in proportions that are distinct from those in the cells from which they are derived. Microvesicles show a relative depletion in microRNA compared with their cells of origin, and are enriched in unusual or novel noncoding RNAs, most of which have no known function. Short-term exposure of brain microvascular endothelial cells to glioma microvesicles results in many gene expression changes in the endothelial cells, most of which cannot be explained by direct delivery of transcripts. Our data suggest that the scope of potential actions of tumor-derived microvesicles is much broader and more complex than previously supposed, and highlight a number of new classes of small RNA that remain to be characterized. © 2013 Landes Bioscience.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1007613
dc.relation.ispartof	RNA Biology	en_US
dc.relation.isbasedon	10.4161/rna.25281	en_US
dc.subject.classification	Developmental Biology	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Endothelial Cells	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Glioma	en_US
dc.subject.mesh	Brain Neoplasms	en_US
dc.subject.mesh	Neovascularization, Pathologic	en_US
dc.subject.mesh	RNA, Messenger	en_US
dc.subject.mesh	RNA, Neoplasm	en_US
dc.subject.mesh	RNA, Untranslated	en_US
dc.subject.mesh	Gene Expression Profiling	en_US
dc.subject.mesh	Gene Expression Regulation, Neoplastic	en_US
dc.subject.mesh	RNA Transport	en_US
dc.subject.mesh	Exosomes	en_US
dc.subject.mesh	Microvessels	en_US
dc.title	Glioma microvesicles carry selectively packaged coding and noncoding RNAs which alter gene expression in recipient cells	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	10	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	0604 Genetics	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	10	en_US

Abstract:

Interactions between glioma cells and their local environment are critical determinants of brain tumor growth, infiltration and neovascularisation. Communication with host cells and stroma via microvesicles represents one pathway by which tumors can modify their surroundings to achieve a tumor-permissive environment. Here we have taken an unbiased approach to identifying RNAs in glioma-derived microvesicles, and explored their potential to regulate gene expression in recipient cells. We find that glioma microvesicles are predominantly of exosomal origin and contain complex populations of coding and noncoding RNAs in proportions that are distinct from those in the cells from which they are derived. Microvesicles show a relative depletion in microRNA compared with their cells of origin, and are enriched in unusual or novel noncoding RNAs, most of which have no known function. Short-term exposure of brain microvascular endothelial cells to glioma microvesicles results in many gene expression changes in the endothelial cells, most of which cannot be explained by direct delivery of transcripts. Our data suggest that the scope of potential actions of tumor-derived microvesicles is much broader and more complex than previously supposed, and highlight a number of new classes of small RNA that remain to be characterized. © 2013 Landes Bioscience.

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http://hdl.handle.net/10453/23658