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SETDB1 的高表达具有预后价值,并促进鼻咽癌中的细胞增殖、迁移和侵袭。

Enhanced expression of SETDB1 possesses prognostic value and promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma.

机构信息

Oncology Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.

Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515.

出版信息

Oncol Rep. 2018 Aug;40(2):1017-1025. doi: 10.3892/or.2018.6490. Epub 2018 Jun 14.

DOI:10.3892/or.2018.6490
PMID:29901162
Abstract

SETDB1, an H3K9‑specific histone methyltransferase, has been described as a repressed transcription marker which triggers tumorigenesis of many types of human cancer. However, there are few studies elucidating the relationship between SETDB1 and nasopharyngeal carcinoma. In the present study, we confirmed that SETDB1 exhibited higher expression levels in nasopharyngeal carcinoma (NPC) tissues and cell lines, compared to these levels in non‑tumor tissues and a normal human nasopharyngeal epithelial cell line. Kaplan‑Meier analysis showed that higher SETDB1 expression indicated an unfavorable prognosis for NPC patients, making it an independent prognostic factor for NPC in the COX proportional hazards model. In vitro functional studies revealed that upregulation of SETDB1 expression in CNE1 cells promoted cell proliferation, possibly through cell cycle G1/S phase transition. Moreover, it also enhanced cell migration and invasion ability. Downregulation of SETDB1 expression in 5‑8F cells resulted in the opposite response. Overall, the findings indicated that increased expression of SETDB1 may predict poor overall survival and the malignant phenotype of NPC.

摘要

SETDB1 是一种 H3K9 特异性组蛋白甲基转移酶,被描述为一种抑制转录的标记物,可引发多种类型的人类癌症发生肿瘤。然而,目前关于 SETDB1 与鼻咽癌之间关系的研究较少。在本研究中,我们证实 SETDB1 在鼻咽癌(NPC)组织和细胞系中的表达水平高于非肿瘤组织和正常的人鼻咽上皮细胞系。Kaplan-Meier 分析表明,SETDB1 表达水平较高提示 NPC 患者预后不良,使其成为 COX 比例风险模型中 NPC 的独立预后因素。体外功能研究表明,上调 CNE1 细胞中 SETDB1 的表达可促进细胞增殖,可能通过细胞周期 G1/S 期转变。此外,它还增强了细胞迁移和侵袭能力。下调 5-8F 细胞中 SETDB1 的表达则产生相反的反应。总体而言,这些发现表明 SETDB1 的表达增加可能预示着 NPC 患者总体生存率和恶性表型较差。

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