Cancer Research Institute, Xiangya School of Medicine, Central South University, Xiangya Road, Changsha, Hunan 410078, China.
Carcinogenesis. 2011 Sep;32(9):1305-14. doi: 10.1093/carcin/bgr174. Epub 2011 Jul 28.
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.
启动子超甲基化导致肿瘤抑制基因（TSGs）沉默是癌症发生的一个标志。氧化还原氮结构域蛋白 1（NOR1）是一个候选 TSG，在鼻咽癌（NPC）中下调。在本研究中，我们鉴定了一个受热休克因子 1 和核呼吸因子 1 调控的功能性 NOR1 启动子。该启动子位于 CpG 岛中。在 NPC 组织样本和癌细胞系中发现了该 CpG 岛的超甲基化，而在非癌性鼻咽组织样本或正常鼻咽上皮细胞中未检测到异常的启动子甲基化。用 5'-氮杂-2'-脱氧胞苷处理 NPC 6-10B 细胞和白血病 HL60 细胞，增加了内源性 NOR1 信使 RNA 的水平。在 NPC HNE1 细胞中外源表达 NOR1 抑制肿瘤细胞集落形成和活力。这些发现表明，启动子超甲基化可能参与 NPC 中 NOR1 基因的转录失活。NOR1 基因在 NPC 中的频繁表观遗传失活表明，它可能是一个关键的肿瘤抑制基因，参与 NPC 的发展。
