Back to Search
Start Over
Hypoxia-induced ebv-circLMP2A promotes angiogenesis in EBV-associated gastric carcinoma through the KHSRP/VHL/HIF1α/VEGFA pathway.
- Source :
-
Cancer Letters . Feb2022, Vol. 526, p259-272. 14p. - Publication Year :
- 2022
-
Abstract
- EBV-encoded circular RNA LMP2A (ebv-circLMP2A) was found to be expressed in EBV-associated gastric carcinoma (EBVaGC) and associated with distant metastasis and poor prognosis. Angiogenesis is a key step in tumor invasion and metastasis and plays a crucial role in tumor progression. However, it is unclear whether and how ebv-circLMP2A is involved in angiogenesis. In this study, we showed that MVD, HIF1α, and VEGFA expression was increased in EBVaGC mouse xenografts with high expression of ebv-circLMP2A. The expression of ebv-circLMP2A was positively correlated with MVD, HIF1α, and VEGFA expression in clinical samples of EBVaGC. Knockdown of ebv-circLMP2A repressed tube formation and migration of HUVECs and decreased VEGFA and HIF1α expression in cancer cells under hypoxia, while ectopic expression of ebv-circLMP2A reversed these effects. Additionally, knockdown of HIF1α blocked the upregulation of ebv-circLMP2A by hypoxia, and ebv-circLMP2A interacted with KHSRP to enhance KHSRP-mediated decay of VHL mRNA, leading to the accumulation of HIF1α under hypoxia. There was a positive feedback loop between HIF1α and ebv-circLMP2A that promotes angiogenesis under hypoxia. ebv-circLMP2A was essential in regulating tumor angiogenesis in EBVaGC and might provide a valuable therapeutic target for EBVaGC. [ABSTRACT FROM AUTHOR]
- Subjects :
- *STOMACH cancer
*NEOVASCULARIZATION
*CIRCULAR RNA
*CANCER invasiveness
*METASTASIS
Subjects
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 526
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 154241538
- Full Text :
- https://doi.org/10.1016/j.canlet.2021.11.031