ARID1A knockdown in human endothelial cells directly induces angiogenesis by regulating angiopoietin-2 secretion and endothelial cell activity
| Autor: | Visith Thongboonkerd, Paleerath Peerapen, Sunisa Yoodee, Sirikanya Plumworasawat |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Tumor suppressor gene
Podosome Angiogenesis Down-Regulation Neovascularization Physiologic 02 engineering and technology Transfection Biochemistry Angiopoietin-2 03 medical and health sciences Cell Movement Structural Biology Humans Gene Silencing RNA Small Interfering Molecular Biology Cell Proliferation 030304 developmental biology Tube formation 0303 health sciences Cell growth Chemistry Antibodies Monoclonal Endothelial Cells Cell migration General Medicine 021001 nanoscience & nanotechnology Cell biology DNA-Binding Proteins Endothelial stem cell HEK293 Cells Gene Knockdown Techniques Podosomes 0210 nano-technology Signal Transduction Transcription Factors |
| Zdroj: | International Journal of Biological Macromolecules. 180:1-13 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2021.02.218 |
| Popis: | AT-rich interactive domain 1A (ARID1A) is a novel tumor suppressor gene found in several human cells and its loss/defect is commonly observed in many cancers. However, its roles in angiogenesis, which is one of the hallmarks for tumor progression, remained unclear. Herein, we demonstrated the direct effects of ARID1A knockdown in human endothelial cells by lentivirus-based short-hairpin RNA (shRNA) (shARID1A) on angiogenesis. Functional assays revealed that shARID1A significantly enhanced cell proliferation and migration/invasion and endothelial tube formation compared with the control cells transfected with scramble shRNA (shControl). Additionally, the shARID1A-transfected cells had significantly increased podosome formation and secretion of angiopoietin-2 (ANG2), a key angiogenic factor. Moreover, neutralization of ANG2 with monoclonal anti-ANG2 antibody strongly reduced cell proliferation and migration/invasion and endothelial tube formation in the shARID1A-transfected cells. These findings indicate that down-regulation of ARID1A in human endothelial cells directly induces angiogenesis by regulating angiopoietin-2 secretion and endothelial cell activity. |
| Databáze: | OpenAIRE |
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