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The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression
- Source :
- Oncotarget
- Publication Year :
- 2015
-
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.
- Subjects :
- 0301 basic medicine
Transcriptional Activation
Small interfering RNA
Angiogenesis
FGF2
Blotting, Western
Enzyme-Linked Immunosorbent Assay
Apoptosis
Fibroblast growth factor
Real-Time Polymerase Chain Reaction
Immunoenzyme Techniques
03 medical and health sciences
angiogenesis
Neuroblastoma
0302 clinical medicine
Cell Movement
Gene expression
Human Umbilical Vein Endothelial Cells
Medicine
Humans
long noncoding RNA
RNA, Messenger
MALAT1
Cells, Cultured
Cell Proliferation
Neovascularization, Pathologic
Cell growth
business.industry
Reverse Transcriptase Polymerase Chain Reaction
Transfection
medicine.disease
Cell biology
Endothelial stem cell
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Immunology
Fibroblast Growth Factor 2
RNA, Long Noncoding
business
Research Paper
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....8995e0fe4f3ea60c73af1f2246cbbbcb