ebv-circRPMS1-p53相互作用在Epstein-Barr病毒相关性胃癌增殖和临床进展中的作用

IF 2.7 4区医学 Q3 VIROLOGY

Virus research Pub Date : 2025-08-20 DOI:10.1016/j.virusres.2025.199617

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

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引用次数: 0

摘要

depstein - barr病毒相关性胃癌（EBVaGC）是一种独特的临床病理实体，具有独特的分子特征，包括潜伏的EBV感染和宿主肿瘤抑制因子的失调。然而，EBV环状rna （EBV - circrnas）和p53蛋白之间的功能相互作用仍然是谜。本研究探讨了ebv-circRPMS1在EBVaGC发病机制中的作用，ebv-circRNA是一种以前未被发现的ebv-circRNA。方法为了明确EBV - circrpms1 - p53的相互作用，在EBV+细胞中siRNA敲低（RT-qPCR验证）可调节EBV - circrpms1。RIP/共免疫沉淀证实ebv-circRPMS1-p53直接结合。EdU检测定量增殖。RNA-FISH/免疫荧光图谱细胞质共定位。异种移植物评估体内致瘤性，而BaseScope/IHC分析组织。临床队列（n = 70）通过Kaplan-Meier /Cox回归将共表达与生存率相关。结果本研究证实ebv-circRPMS1直接与p53结合，从而促进肿瘤增殖。临床上，ebv-circRPMS1-p53共表达与EBVaGC患者的低生存率相关。这些发现揭示了一种新的破坏宿主肿瘤抑制的病毒策略，为靶向ebv-circRPMS1-p53轴在精确肿瘤学中的应用提供了理论依据。

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

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.

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来源期刊

Virus research 医学-病毒学

CiteScore

9.50

自引率

2.00%

发文量

239

审稿时长

43 days

期刊介绍： Virus Research provides a means of fast publication for original papers on fundamental research in virology. Contributions on new developments concerning virus structure, replication, pathogenesis and evolution are encouraged. These include reports describing virus morphology, the function and antigenic analysis of virus structural components, virus genome structure and expression, analysis on virus replication processes, virus evolution in connection with antiviral interventions, effects of viruses on their host cells, particularly on the immune system, and the pathogenesis of virus infections, including oncogene activation and transduction.