Department of Clinical Medicine, Grade 20, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, China.
Cancer Research Institute of Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, China.
Curr Cancer Drug Targets. 2024;24(2):127-141. doi: 10.2174/1568009623666230512153741.
EBV promotes many cancers such as lymphoma, nasopharyngeal carcinoma, and gastric; Latent Membrane Protein 1 (LMP1) is considered to be a major oncogenic protein encoded by Epstein- Barr virus (EBV). LMP1 functions as a carcinogen in lymphoma and nasopharyngeal carcinoma, and LMP1 may also promote gastric cancer. The expression level of LMP1 in host cells is a key determinant in tumorigenesis and maintenance of virus specificity. By promoting cell immortalization and cell transformation, promoting cell proliferation, affecting immunity, and regulating cell apoptosis, LMP1 plays a crucial tumorigenic role in epithelial cancers. However, very little is currently known about LMP1 in Epstein-Barr virus-associated gastric cancer (EBVaGC); the main reason is that the expression level of LMP1 in EBVaGC is comparatively lower than other EBV-encoded proteins, such as The Latent Membrane Protein 2A (LMP2A), Epstein-Barr nuclear antigen 1 (EBNA1) and BamHI-A rightward frame 1 (BARF1), to date, there are few studies related to LMP1 in EBVaGC. Recent studies have demonstrated that LMP1 promotes EBVaGC by affecting The phosphatidylinositol 3-kinase- Akt (PI3K-Akt), Nuclear factor-kappa B (NF-κB), and other signaling pathways to regulate many downstream targets such as Forkhead box class O (FOXO), C-X-C-motif chemokine receptor (CXCR), COX-2 (Cyclooxygenase-2); moreover, the gene methylation induced by LMP1 in EBVaGC has become one of the characteristics that distinguish this gastric cancer (GC) from other types of gastric cancer and LMP1 also promotes the formation of the tumor microenvironment (TME) of EBVaGC in several ways. This review synthesizes previous relevant literature, aiming to highlight the latest findings on the mechanism of action of LMP1 in EBVaGC, summarize the function of LMP1 in EBVaGC, lay the theoretical foundation for subsequent new research on LMP1 in EBVaGC, and contribute to the development of novel LMP1-targeted drugs.
EBV 可促进多种癌症的发生，如淋巴瘤、鼻咽癌和胃癌；潜伏膜蛋白 1（LMP1）被认为是 Epstein-Barr 病毒（EBV）编码的主要致癌蛋白。LMP1 在淋巴瘤和鼻咽癌中作为致癌基因发挥作用，LMP1 也可能促进胃癌的发生。宿主细胞中 LMP1 的表达水平是决定肿瘤发生和病毒特异性维持的关键因素。LMP1 通过促进细胞永生化和转化、促进细胞增殖、影响免疫和调节细胞凋亡，在上皮性癌中发挥关键的致癌作用。然而，目前对于 EBV 相关胃癌（EBVaGC）中 LMP1 的了解甚少；主要原因是 LMP1 在 EBVaGC 中的表达水平相对低于其他 EBV 编码蛋白，如潜伏膜蛋白 2A（LMP2A）、EB 核抗原 1（EBNA1）和 BamHI-A 右向框 1（BARF1），迄今为止，与 EBVaGC 中 LMP1 相关的研究较少。最近的研究表明，LMP1 通过影响磷脂酰肌醇 3-激酶- Akt（PI3K-Akt）、核因子-κB（NF-κB）等信号通路，调节叉头框 O 类（FOXO）、C-X-C 基序趋化因子受体（CXCR）、环氧化酶-2（COX-2）等许多下游靶标，促进 EBVaGC 的发生；此外，LMP1 在 EBVaGC 中诱导的基因甲基化已成为区分这种胃癌（GC）与其他类型胃癌的特征之一，LMP1 还通过多种方式促进 EBVaGC 肿瘤微环境（TME）的形成。本综述综合了以往相关文献，旨在强调 LMP1 在 EBVaGC 中的作用机制的最新研究结果，总结 LMP1 在 EBVaGC 中的功能，为后续研究 LMP1 在 EBVaGC 中的作用奠定理论基础，并为新型 LMP1 靶向药物的开发做出贡献。
