Epstein-Barr virus-derived circular RNA LMP2A induces stemness in EBV-associated gastric cancer
© 2020 The Authors..
Cancer stem cells (CSCs) are cancer-initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear. Here, NOD/SCID mice were injected subcutaneously with the EBVaGC cell line SNU719 and treated with 5-fluorouracil weekly. Successive generations of xenografts yielded a highly malignant EBVaGC cell line, SNU-4th, which displays properties of CSCs and mainly consists of CD44+ CD24- cells. In SNU-4th cells, an EBV-encoded circRNA, ebv-circLMP2A, expression increased and plays crucial roles in inducing and maintaining stemness phenotypes through targeting miR-3908/TRIM59/p53 axis. Additionally, high expression of ebv-circLMP2A is significantly associated with metastasis and poor prognosis in patients with EBVaGC. These findings not only provide evidence for the existence of CSCs in EBVaGC and elucidate the pathogenic mechanism of ebv-circLMP2A in EBVaGC, but also provide a promising therapeutic target for EBVaGC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
EMBO reports - 21(2020), 10 vom: 05. Okt., Seite e49689 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gong, Li-Ping [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.04.2021 Date Revised 31.05.2022 published: Print-Electronic GEO: GSE145894 Citation Status MEDLINE |
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| doi: |
10.15252/embr.201949689 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31364733X |
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| 100 | 1 | |a Gong, Li-Ping |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Epstein-Barr virus-derived circular RNA LMP2A induces stemness in EBV-associated gastric cancer |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 27.04.2021 | ||
| 500 | |a Date Revised 31.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a GEO: GSE145894 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Authors. | ||
| 520 | |a Cancer stem cells (CSCs) are cancer-initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear. Here, NOD/SCID mice were injected subcutaneously with the EBVaGC cell line SNU719 and treated with 5-fluorouracil weekly. Successive generations of xenografts yielded a highly malignant EBVaGC cell line, SNU-4th, which displays properties of CSCs and mainly consists of CD44+ CD24- cells. In SNU-4th cells, an EBV-encoded circRNA, ebv-circLMP2A, expression increased and plays crucial roles in inducing and maintaining stemness phenotypes through targeting miR-3908/TRIM59/p53 axis. Additionally, high expression of ebv-circLMP2A is significantly associated with metastasis and poor prognosis in patients with EBVaGC. These findings not only provide evidence for the existence of CSCs in EBVaGC and elucidate the pathogenic mechanism of ebv-circLMP2A in EBVaGC, but also provide a promising therapeutic target for EBVaGC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a EBV | |
| 650 | 4 | |a cancer stem cells | |
| 650 | 4 | |a circular RNA | |
| 650 | 4 | |a gastric carcinoma | |
| 650 | 4 | |a miR-3908 | |
| 650 | 7 | |a Intracellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a RNA, Circular |2 NLM | |
| 650 | 7 | |a TRIM59 protein, human |2 NLM | |
| 650 | 7 | |a Tripartite Motif Proteins |2 NLM | |
| 700 | 1 | |a Chen, Jian-Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Zhen-Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Zhi-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Yu-Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jing-Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Bi, Yuan-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jun-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Chun-Kui |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:21 |g year:2020 |g number:10 |g day:05 |g month:10 |g pages:e49689 |
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