Department of Pathogenic Biology, Qingdao University Medical College, 38 Dengzhou Road, Qingdao, 266021, China.
Department of Pathogenic Biology, Qingdao University Medical College, 38 Dengzhou Road, Qingdao, 266021, China; Department of Clinical Laboratory, Central Hospital of Zibo, 54 Gongqingtuan Road, Zibo, 255036, China.
Virology. 2020 Feb;541:63-74. doi: 10.1016/j.virol.2019.12.004. Epub 2019 Dec 11.
GCNT3 (core 2β-1,6-acetylglucosaminyltransferase) is a novel core mucin synthase. It is known that abnormal expression of GCNT3 promotes the progression of several human cancers. However, its relationship with Epstein-Barr virus (EBV) has not been comprehensively studied. We found GCNT3 expression in EBV-associated gastric cancer cells and tissues to be lower than in EBV-negative gastric cancer cells and tissues, and high expression was significantly associated with advanced tumor-lymph node metastasis. Luciferase reporter assay revealed that miR-BART1-5p directly targeted GCNT3. In addition, miR-BART1-5p mimics transfection was observed to reduce cell proliferation and migration, while miR-BART1-5p inhibitor increased cell proliferation and migration following transfection. In conclusion, both miR-BART1-5p and knockdown of GCNT3 inhibited cell proliferation and migration. In addition, EBV may regulate GCNT3 by affecting the NF-kB signaling pathway. E-cadherin, N-cadherin, vimentin, and p-ERK were found to be downstream molecules of the miR-BART1-5p/GCNT3 pathway.
GCNT3(核心 2β-1,6-乙酰氨基葡萄糖基转移酶)是一种新型的核心粘蛋白合成酶。已知 GCNT3 的异常表达会促进几种人类癌症的进展。然而,其与 Epstein-Barr 病毒(EBV)的关系尚未得到全面研究。我们发现 EBV 相关胃癌细胞和组织中的 GCNT3 表达低于 EBV 阴性胃癌细胞和组织,高表达与肿瘤-淋巴结转移的进展显著相关。荧光素酶报告基因检测显示,miR-BART1-5p 可直接靶向 GCNT3。此外,miR-BART1-5p 模拟物转染观察到细胞增殖和迁移减少,而 miR-BART1-5p 抑制剂转染后细胞增殖和迁移增加。总之,miR-BART1-5p 和 GCNT3 的敲低均抑制了细胞增殖和迁移。此外,EBV 可能通过影响 NF-kB 信号通路来调节 GCNT3。发现 E-cadherin、N-cadherin、波形蛋白和 p-ERK 是 miR-BART1-5p/GCNT3 通路的下游分子。