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miR-BART1-5p 通过靶向核心 2β-1,6-乙酰氨基葡萄糖基转移酶 GCNT3 抑制 EBV 相关胃癌中的细胞增殖和迁移。

MiR-BART1-5p targets core 2β-1,6-acetylglucosaminyltransferase GCNT3 to inhibit cell proliferation and migration in EBV-associated gastric cancer.

机构信息

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.

出版信息

Virology. 2020 Feb;541:63-74. doi: 10.1016/j.virol.2019.12.004. Epub 2019 Dec 11.

Abstract

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.

摘要

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。

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