PUBLICATION
Aberrant ceRNA-mediated regulation of KNG1 contributes to glioblastoma-induced angiogenesis
- Authors
- Ren, Y., Ji, N., Kang, X., Wang, R., Ma, W., Hu, Z., Liu, X., Wang, Y.
- ID
- ZDB-PUB-161025-20
- Date
- 2016
- Source
- Oncotarget : (Journal)
- Registered Authors
- Keywords
- angiogenesis, ceRNA, exosome, glioblastoma, kininogen
- MeSH Terms
- none
- PubMed
- none Full text @ Oncotarget
Citation
Ren, Y., Ji, N., Kang, X., Wang, R., Ma, W., Hu, Z., Liu, X., Wang, Y. (2016) Aberrant ceRNA-mediated regulation of KNG1 contributes to glioblastoma-induced angiogenesis. Oncotarget. .
Abstract
Glioblastoma is a highly vascularized brain tumor that causes high mortality. Kininogen-1 (KNG1) has demonstrated both tumor suppressor and antiangiogenesis properties in gliobastoma cells. We analyzed the microarray and proteomic profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the KNG1. Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR-138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0.05 for all), which resulted in the upregulation of oncogenic EGFR signaling in both cell lines, and stimulated angiogenic processes in cultured iHECs and zebrafish and mouse xenograft models of glioblastoma-induced angiogenesis. Angiogenic transduction of iHECs occurred via the uptake of U87-derived exosomes enriched in miR-138, with the siRNA-mediated knockdown of KNG1, CTU1, KIAA1274, or RAX increasing the level of miR-138 enrichment to varying extents and enhancing the angiogenic effects of the U87-derived exosomes on iHECs. The competing endogenous RNA network of KNG1 represents potential targets for the development of novel therapeutic strategies for glioblastoma.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping