EBV-circRPMS1与p53相互作用在爱泼斯坦-巴尔病毒相关胃癌增殖及临床进展中的作用

Role of ebv-circRPMS1-p53 interaction in the proliferation and clinical progression of Epstein-Barr virus-associated gastric carcinoma.

作者信息

Yang Ling, Li Meini, Xie Guiming, Wu Xian, Qin Mingxiong, Guo Birong, Zhang Jingyue

机构信息

Department of Clinical Laboratory, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People's Hospital, Guigang, Guangxi, China.

Department of Pathology, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People's Hospital, Guigang, Guangxi, China.

出版信息

Virus Res. 2025 Aug 20;360:199617. doi: 10.1016/j.virusres.2025.199617.

DOI:10.1016/j.virusres.2025.199617

PMID:40846151

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12398897/

Abstract

BACKGROUND

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) represents a distinct clinicopathological entity with unique molecular characteristics, including latent EBV infection and dysregulation of host tumor suppressors. However, the functional interplay between EBV circular RNAs (ebv-circRNAs) and p53 protein remains enigmatic. This study explored the role of ebv-circRPMS1, a previously uncharacterized ebv-circRNA, in EBVaGC pathogenesis.

METHODS

To define ebv-circRPMS1-p53 interplay, siRNA knockdown (validated by RT-qPCR) modulated ebv-circRPMS1 in EBV+ cells. RIP/co-immunoprecipitation confirmed direct ebv-circRPMS1-p53 binding. EdU assays quantified proliferation. RNA-FISH/immunofluorescence mapped cytoplasmic colocalization. Xenografts evaluated in vivo tumorigenicity, while BaseScope/IHC analyzed tissues. Clinical cohort (n = 70) correlated co-expression with survival via Kaplan-Meier/Cox regression.

RESULTS

This study demonstrated that ebv-circRPMS1 directly binds to p53, thereby enhancing tumor proliferation. Clinically, ebv-circRPMS1-p53 co-expression correlates with poor survival in EBVaGC patients.

CONCLUSIONS

These findings unveil a novel viral strategy for subverting host tumor suppression, providing a rationale for targeting the ebv-circRPMS1-p53 axis in precision oncology.

摘要

背景

爱泼斯坦-巴尔病毒相关胃癌（EBVaGC）是一种具有独特分子特征的独特临床病理实体，包括潜伏性EBV感染和宿主肿瘤抑制因子的失调。然而，EBV环状RNA（ebv-circRNAs）与p53蛋白之间的功能相互作用仍不清楚。本研究探讨了一种以前未被描述的ebv-circRNA——ebv-circRPMS1在EBVaGC发病机制中的作用。

方法

为了确定ebv-circRPMS1与p53的相互作用，通过小干扰RNA敲低（经逆转录定量聚合酶链反应验证）来调节EBV阳性细胞中的ebv-circRPMS1。RNA免疫沉淀/免疫共沉淀证实了ebv-circRPMS1与p53的直接结合。EdU检测定量细胞增殖。RNA荧光原位杂交/免疫荧光确定细胞质中的共定位。异种移植评估体内致瘤性，而原位杂交/免疫组化分析组织。临床队列（n = 70）通过Kaplan-Meier法/Cox回归分析共表达与生存率的相关性。