The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression

Tee, AE; Liu, B; Song, R; Li, J; Pasquier, E; Cheung, BB; Jiang, C; Marshall, GM; Haber, M; Norris, MD; Fletcher, JI; Dinger, ME; Liu, T

The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression

Tee, AE Liu, B Song, R Li, J

Pasquier, E Cheung, BB Jiang, C Marshall, GM Haber, M Norris, MD Fletcher, JI Dinger, ME Liu, T

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Publication Type:: Journal Article
Citation:: Oncotarget, 2016, 7 (8), pp. 8663 - 8675
Issue Date:: 2016-01-01

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Field	Value	Language
dc.contributor.author	Tee, AE	en_US
dc.contributor.author	Liu, B	en_US
dc.contributor.author	Song, R	en_US
dc.contributor.author	Li, J https://orcid.org/0000-0003-1833-7413	en_US
dc.contributor.author	Pasquier, E	en_US
dc.contributor.author	Cheung, BB	en_US
dc.contributor.author	Jiang, C	en_US
dc.contributor.author	Marshall, GM	en_US
dc.contributor.author	Haber, M	en_US
dc.contributor.author	Norris, MD	en_US
dc.contributor.author	Fletcher, JI	en_US
dc.contributor.author	Dinger, ME	en_US
dc.contributor.author	Liu, T	en_US
dc.date.available	2015-12-07	en_US
dc.date.issued	2016-01-01	en_US
dc.identifier.citation	Oncotarget, 2016, 7 (8), pp. 8663 - 8675	en_US
dc.identifier.uri	http://hdl.handle.net/10453/117231
dc.description.abstract	Neuroblastoma is the most common solid tumor during early childhood. One of the key features of neuroblastoma is extensive tumor-driven angiogenesis due to hypoxia. However, the mechanism through which neuroblastoma cells drive angiogenesis is poorly understood. Here we show that the long noncoding RNA MALAT1 was upregulated in human neuroblastoma cell lines under hypoxic conditions. Conditioned media from neuroblastoma cells transfected with small interfering RNAs (siRNA) targeting MALAT1, compared with conditioned media from neuroblastoma cells transfected with control siRNAs, induced significantly less endothelial cell migration, invasion and vasculature formation. Microarray-based differential gene expression analysis showed that one of the genes most significantly downregulated following MALAT1 suppression in human neuroblastoma cells under hypoxic conditions was fibroblast growth factor 2 (FGF2). RT-PCR and immunoblot analyses confirmed that MALAT1 suppression reduced FGF2 expression, and Enzyme-Linked Immunosorbent Assays revealed that transfection with MALAT1 siRNAs reduced FGF2 protein secretion from neuroblastoma cells. Importantly, addition of recombinant FGF2 protein to the cell culture media reversed the effects of MALAT1 siRNA on vasculature formation. Taken together, our data suggest that up-regulation of MALAT1 expression in human neuroblastoma cells under hypoxic conditions increases FGF2 expression and promotes vasculature formation, and therefore plays an important role in tumor-driven angiogenesis.	en_US
dc.relation.ispartof	Oncotarget	en_US
dc.relation.isbasedon	10.18632/oncotarget.6675	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Neuroblastoma	en_US
dc.subject.mesh	Neovascularization, Pathologic	en_US
dc.subject.mesh	Fibroblast Growth Factor 2	en_US
dc.subject.mesh	RNA, Messenger	en_US
dc.subject.mesh	Blotting, Western	en_US
dc.subject.mesh	Immunoenzyme Techniques	en_US
dc.subject.mesh	Enzyme-Linked Immunosorbent Assay	en_US
dc.subject.mesh	Reverse Transcriptase Polymerase Chain Reaction	en_US
dc.subject.mesh	Apoptosis	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Cell Movement	en_US
dc.subject.mesh	Gene Expression Regulation, Neoplastic	en_US
dc.subject.mesh	Transcriptional Activation	en_US
dc.subject.mesh	Human Umbilical Vein Endothelial Cells	en_US
dc.subject.mesh	Real-Time Polymerase Chain Reaction	en_US
dc.subject.mesh	RNA, Long Noncoding	en_US
dc.title	The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	7	en_US
utslib.for	1112 Oncology and Carcinogenesis	en_US
utslib.for	0601 Biochemistry and Cell Biology	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 Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - AAI - Advanced Analytics Institute Research Centre
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Students
utslib.copyright.status	open_access
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	7	en_US

Abstract:

Neuroblastoma is the most common solid tumor during early childhood. One of the key features of neuroblastoma is extensive tumor-driven angiogenesis due to hypoxia. However, the mechanism through which neuroblastoma cells drive angiogenesis is poorly understood. Here we show that the long noncoding RNA MALAT1 was upregulated in human neuroblastoma cell lines under hypoxic conditions. Conditioned media from neuroblastoma cells transfected with small interfering RNAs (siRNA) targeting MALAT1, compared with conditioned media from neuroblastoma cells transfected with control siRNAs, induced significantly less endothelial cell migration, invasion and vasculature formation. Microarray-based differential gene expression analysis showed that one of the genes most significantly downregulated following MALAT1 suppression in human neuroblastoma cells under hypoxic conditions was fibroblast growth factor 2 (FGF2). RT-PCR and immunoblot analyses confirmed that MALAT1 suppression reduced FGF2 expression, and Enzyme-Linked Immunosorbent Assays revealed that transfection with MALAT1 siRNAs reduced FGF2 protein secretion from neuroblastoma cells. Importantly, addition of recombinant FGF2 protein to the cell culture media reversed the effects of MALAT1 siRNA on vasculature formation. Taken together, our data suggest that up-regulation of MALAT1 expression in human neuroblastoma cells under hypoxic conditions increases FGF2 expression and promotes vasculature formation, and therefore plays an important role in tumor-driven angiogenesis.

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http://hdl.handle.net/10453/117231