The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression.
- Impact Journals
- Publication Type:
- Journal Article
- Oncotarget, 2016, 7 (8), pp. 8663 - 8675
- Issue Date:
|dc.identifier.citation||Oncotarget, 2016, 7 (8), pp. 8663 - 8675||en_US|
|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 down-regulated 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.subject.mesh||Enzyme-Linked Immunosorbent Assay||en_US|
|dc.subject.mesh||Fibroblast Growth Factor 2||en_US|
|dc.subject.mesh||Gene Expression Regulation, Neoplastic||en_US|
|dc.subject.mesh||Human Umbilical Vein Endothelial Cells||en_US|
|dc.subject.mesh||RNA, Long Noncoding||en_US|
|dc.subject.mesh||Real-Time Polymerase Chain Reaction||en_US|
|dc.subject.mesh||Reverse Transcriptase Polymerase Chain Reaction||en_US|
|dc.title||The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression.||en_US|
|utslib.for||0801 Artificial Intelligence and Image Processing||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|
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