Epstein-Barr Virus-derived Circular RNA LMP2A Induces Stemness in EBV-associated Gastric Cancer

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2020 Aug 14

PMID 32790025

Citations 48

Authors

Li-Ping Gong

Jian-Ning Chen

Min Dong

Zhen-Dong Xiao

Zhi-Ying Feng

Yu-Hang Pan

Yu Zhang

Yu Du

Jing-Yue Zhang

Yuan-Hua Bi

Jun-Ting Huang

Jing Liang

Chun-Kui Shao

Affiliations

Soon will be listed here.

Abstract

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.

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