E-viri
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Gong, Li‐ping; Chen, Jian‐ning; Dong, Min; Xiao, Zhen‐dong; Feng, Zhi‐ying; Pan, Yu‐hang; Zhang, Yu; Du, Yu; Zhang, Jing‐yue; Bi, Yuan‐hua; Huang, Jun‐ting; Liang, Jing; Shao, Chun‐kui
EMBO reports, 05 October 2020, Letnik: 21, Številka: 10Journal Article
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. Synopsis The circRNA LMP2A produced by the Epstein‐Barr virus induces stemness of EBV‐associated gastric cancer cells by attenuating the tumor suppressive effect of the miR‐3908/TRIM59/p53 axis, thereby promoting metastasis and tumor progression. Cells with properties of cancer stem cells were isolated form EBV‐associated gastric cancer (EBVaGC). The levels of an EBV‐encoded circRNA (ebv‐circLMP2A) are significantly increased in EBVaGC. ebv‐circLMP2A has crucial roles in inducing and maintaining cancer stemness in EBVaGC. High expression of ebv‐circLMP2A is significantly associated with metastasis and poor prognosis in EBVaGC patients. The circRNA LMP2A produced by the Epstein‐Barr virus induces stemness of EBV‐associated gastric cancer cells by attenuating the tumor suppressive effect of the miR‐3908/TRIM59/p53 axis, thereby promoting metastasis and tumor progression.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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