关键词: Epstein-Barr virus GCNT3 LMP2A mTORC1

Mesh : Humans Nasopharyngeal Carcinoma / genetics virology pathology metabolism Nasopharyngeal Neoplasms / genetics virology pathology metabolism Viral Matrix Proteins / genetics metabolism Cell Line, Tumor Cell Movement / genetics Cell Proliferation N-Acetylglucosaminyltransferases / genetics metabolism Mechanistic Target of Rapamycin Complex 1 / metabolism genetics Gene Expression Regulation, Neoplastic Herpesvirus 4, Human / genetics Zinc Finger E-box-Binding Homeobox 1 / genetics metabolism Epithelial-Mesenchymal Transition / genetics

来  源:   DOI:10.1007/s11262-024-02071-w

Abstract:
O-Glycan synthesis enzyme glucosaminyl (N-acetyl) transferase 3 (GCNT3) is closely related to the occurrence and development of various cancers. However, the regulatory mechanism and function of GCNT3 in nasopharyngeal carcinoma (NPC) are still poorly understood. This study aims to explore the regulatory mechanism of EBV-encoded latent membrane protein 2A (LMP2A) on GCNT3 and the biological role of GCNT3 in NPC. The results show that LMP2A can activate GCNT3 through the mTORC1 pathway, and there is a positive feedback between the mTORC1 and GCNT3. GCNT3 regulates EMT progression by forming a complex with ZEB1 to promote cell migration. GCNT3 can also promote cell proliferation. These findings indicate that targeting the LMP2A-mTORC1-GCNT3 axis may represent a novel therapeutic target in NPC.
摘要:
O-聚糖合成酶氨基葡萄糖(N-乙酰)转移酶3(GCNT3)与多种肿瘤的发生发展密切相关。然而,GCNT3在鼻咽癌(NPC)中的调控机制和功能尚不清楚。本研究旨在探讨EBV编码的潜伏膜蛋白2A(LMP2A)对GCNT3的调控机制及GCNT3在鼻咽癌中的生物学作用。结果表明,LMP2A可以通过mTORC1通路激活GCNT3,mTORC1和GCNT3之间存在正反馈。GCNT3通过与ZEB1形成复合物以促进细胞迁移来调节EMT进程。GCNT3还可以促进细胞增殖。这些发现表明靶向LMP2A-mTORC1-GCNT3轴可能代表NPC中的新治疗靶标。
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