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EBV 相关鼻咽癌中单胺氧化酶 A 下调。

Monoamine oxidase A is down-regulated in EBV-associated nasopharyngeal carcinoma.

机构信息

Department of Oral and Craniofacial Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.

Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.

出版信息

Sci Rep. 2020 Apr 9;10(1):6115. doi: 10.1038/s41598-020-63150-0.

Abstract

Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we identify for the first time a role for monoamine oxidase A (MAOA) in NPC. MAOA is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines. Depending on the cancer type, MAOA can either have a tumour-promoting or tumour-suppressive role. We show that MAOA is down-regulated in primary NPC tissues and its down-regulation enhances the migration of NPC cells. In addition, we found that EBV infection can down-regulate MAOA expression in both pre-malignant and malignant nasopharyngeal epithelial (NPE) cells. We further demonstrate that MAOA is down-regulated as a result of IL-6/IL-6R/STAT3 signalling and epigenetic mechanisms, effects that might be attributed to EBV infection in NPE cells. Taken together, our data point to a central role for EBV in mediating the tumour suppressive effects of MAOA and that loss of MAOA could be an important step in the pathogenesis of NPC.

摘要

鼻咽癌(NPC)是一种高度转移性癌症,与 Epstein-Barr 病毒(EBV)感染密切相关。在这项研究中,我们首次发现单胺氧化酶 A(MAOA)在 NPC 中的作用。MAOA 是一种线粒体酶,可催化神经递质和膳食胺的氧化脱氨作用。根据癌症类型的不同,MAOA 可能具有促进肿瘤或抑制肿瘤的作用。我们发现 MAOA 在原发性 NPC 组织中下调,其下调可增强 NPC 细胞的迁移。此外,我们发现 EBV 感染可下调鼻咽上皮(NPE)细胞中前恶性和恶性的 MAOA 表达。我们进一步证明,MAOA 的下调是由 IL-6/IL-6R/STAT3 信号和表观遗传机制引起的,这些效应可能归因于 NPE 细胞中的 EBV 感染。综上所述,我们的数据表明 EBV 在介导 MAOA 的肿瘤抑制作用中起核心作用,MAOA 的缺失可能是 NPC 发病机制中的一个重要步骤。

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