NOR1 is an HSF1-and NRF1-regulated putative tumor suppressor inactivated by promoter hypermethylation in nasopharyngeal carcinoma
NOR1 is an HSF1-and NRF1-regulated putative tumor suppressor inactivated by promoter hypermethylation in nasopharyngeal carcinoma
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NOR1 是一种 HSF1 和 NRF1 调节的推定肿瘤抑制因子，在鼻咽癌中因启动子高甲基化而失活
DOI：
10.1093/carcin/bgr174
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发表时间：
2011-09-01
期刊：
影响因子：
4.7
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
--
作者：
Li, Wenjuan;Li, Xiaoling;Li, Guiyuan
启动子高甲基化介导的肿瘤抑制基因(TSG)沉默是肿瘤发生的标志。氧化硝基结构域含蛋白1(Nor1)是鼻咽癌中下调表达的候选TSG。在本研究中，我们发现了一个受热休克因子1和核呼吸因子1调控的Nor1启动子。该启动子位于CpG岛上。在鼻咽癌组织和癌细胞系中发现该CpG岛的高甲基化，而在非癌鼻咽组织和正常鼻咽上皮细胞中未检测到异常的启动子甲基化。5‘-氮杂-2’-脱氧胞苷作用于鼻咽癌6-10B细胞和白血病HL60细胞可增加Nor1信使RNA的内源性水平。Nor1基因在鼻咽癌HNE1细胞中的异位表达抑制了肿瘤细胞的集落形成和存活。这些结果提示，启动子高甲基化可能参与了鼻咽癌Nor1基因的转录失活。Nor1基因在鼻咽癌中频繁的表观遗传失活，提示它可能是鼻咽癌发生发展过程中的一个重要的肿瘤抑制因子。
Promoter hypermethylation-mediated silencing of tumor suppressor genes (TSGs) is a hallmark of oncogenesis. Oxidored-nitro domain-containing protein 1 (NOR1) is a candidate TSG that is downregulated in nasopharyngeal carcinoma (NPC). In the present study, we identified a functional NOR1 promoter that is regulated by heat shock factor 1 and nuclear respiratory factor 1. The promoter is located within a CpG island. Hypermethylation of this CpG island was found in NPC tissue samples and cancer cell lines, whereas no aberrant promoter methylation was detected in non-cancerous nasopharyngeal tissue samples or normal nasopharyngeal epithelial cells. Treatment of NPC 6-10B cells and leukemia HL60 cells with 5'-aza-2'-deoxycytidine increased endogenous levels of NOR1 messenger RNA. Ectopic expression of NOR1 in NPC HNE1 cells inhibited tumor cell colony formation and viability. These findings suggest that promoter hypermethylation may participate in transcriptional inactivation of the NOR1 gene in NPC. Frequent epigenetic inactivation of the NOR1 gene in NPC suggests that it may be a critical tumor suppressor involved in the development of NPC.