Hypoxia-induced ebv-circLMP2A promotes angiogenesis in EBV-associated gastric carcinoma through the KHSRP/VHL/HIF1α/VEGFA pathway
Copyright © 2021 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:526 |
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| Enthalten in: |
Cancer letters - 526(2022) vom: 01. Feb., Seite 259-272 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Du, Yu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.02.2022 Date Revised 01.02.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.canlet.2021.11.031 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM334006260 |
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| 100 | 1 | |a Du, Yu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hypoxia-induced ebv-circLMP2A promotes angiogenesis in EBV-associated gastric carcinoma through the KHSRP/VHL/HIF1α/VEGFA pathway |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 01.02.2022 | ||
| 500 | |a Date Revised 01.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Angiogenesis | |
| 650 | 4 | |a Circular RNA | |
| 650 | 4 | |a EBV | |
| 650 | 4 | |a Gastric carcinoma | |
| 650 | 4 | |a HIF1α | |
| 650 | 7 | |a KHSRP protein, human |2 NLM | |
| 650 | 7 | |a RNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a Trans-Activators |2 NLM | |
| 650 | 7 | |a VEGFA protein, human |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor A |2 NLM | |
| 650 | 7 | |a Von Hippel-Lindau Tumor Suppressor Protein |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 650 | 7 | |a VHL protein, human |2 NLM | |
| 650 | 7 | |a EC 6.3.2.- |2 NLM | |
| 700 | 1 | |a Zhang, Jing-Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Li-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Zhi-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Deyu |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Yu-Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Li-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Jing-Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Gao-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jian-Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Chun-Kui |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:526 |g year:2022 |g day:01 |g month:02 |g pages:259-272 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.canlet.2021.11.031 |3 Volltext |
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