氧化还原硝基结构域蛋白 1（NOR1）的表达抑制鼻咽癌中的 slug/vimentin，但不抑制 snail：在体外和体内抑制 EMT 作用。

Oxidored-nitro domain containing protein 1 (NOR1) expression suppresses slug/vimentin but not snail in nasopharyngeal carcinoma: Inhibition of EMT in vitro and in vivo in mice.

机构信息

Hunan Provincial Tumor Hospital and The Tumor Hospital Affiliated to Xiangya School of Medicine, The Central South University, Changsha, Hunan 410013, China; Cancer Research Institute, Xiangya School of Medicine, The Central South University, Changsha 410078, China.

Cancer Research Institute, Xiangya School of Medicine, The Central South University, Changsha 410078, China.

出版信息

Cancer Lett. 2014 Jun 28;348(1-2):109-18. doi: 10.1016/j.canlet.2014.03.005. Epub 2014 Mar 18.

DOI:10.1016/j.canlet.2014.03.005

PMID:24657653

Abstract

Oxidored-nitro domain containing protein 1 (NOR1) is a putative tumor suppressor gene. In this study, NOR1 expression was detected in NPC tissues and non-cancerous nasopharyngeal epithelium. The data showed that NOR1 protein was decreased in NPC tissues. Lost expression NOR1 protein was associated with poor overall and event-free survival of NPC patients. Overexpression of NOR1 in NPC cells resulted in a significant morphological change and decreased expression of epithelial-to-mesenchymal transition (EMT) mediators (e.g., slug and vimentin), but induced cytokeratin 13 expression. A nude mouse metastasis assay revealed that overexpression of NOR1 decreased NPC tumor cells metastasis capacity in vivo. Knockdown of NOR1 expression in HeLa cells was sufficient to abrogate epithelial traits and to enhance cell migration and invasion. Concomitant inhibition of slug or vimentin alleviated induction of EMT, migration or invasion by NOR1 siRNA in HeLa cells in vitro. In conclusion, the data from the current study suggest, for the first time, that NOR1 plays an important role in NPC in ex vivo, in vitro, and in vivo.

摘要

氧化还原酶结构域包含蛋白 1（NOR1）是一种假定的肿瘤抑制基因。在这项研究中，检测了 NPC 组织和非癌性鼻咽上皮中的 NOR1 表达。数据显示，NOR1 蛋白在 NPC 组织中减少。NOR1 蛋白的表达缺失与 NPC 患者的总生存率和无事件生存率差有关。NOR1 在 NPC 细胞中的过表达导致显著的形态变化和上皮间质转化（EMT）介质（如 slug 和波形蛋白）的表达降低，但诱导角蛋白 13 的表达。裸鼠转移实验显示，NOR1 的过表达降低了 NPC 肿瘤细胞在体内的转移能力。在 HeLa 细胞中敲低 NOR1 的表达足以消除上皮特征，并增强细胞迁移和侵袭。体外实验中，同时抑制 slug 或波形蛋白可减轻 NOR1 siRNA 诱导的 EMT、迁移或侵袭。总之，本研究首次表明，NOR1 在 NPC 的离体、体外和体内均发挥重要作用。