NOR1 is an HSF1- and NRF1-regulated putative tumor suppressor inactivated by promoter hypermethylation in nasopharyngeal carcinoma

Wenjuan Li, Xiaoling Li, Wei Wang, Xiayu Li, Yixin Tan, Mei Yi, Jianbo Yang, James B. McCarthy, Wei Xiong, Minghua Wu, Jian Ma, Bo Su, Zuping Zhang, Qianjin Liao, Bo Xiang, Guiyuan Li

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38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1305-1314
Number of pages10
JournalCarcinogenesis
Volume32
Issue number9
DOIs
StatePublished - 2011

Bibliographical note

Funding Information:
National High-tech R&D Program (863 Program) of China (No. 2007AA02Z170); the National Natural Science Foundation of China (Nos. 81000883, 30971147, 30871282, 30871365, 81072270); the National ‘111’ Project of China (No.111-2-12); Natural Science Foundation of Hunan Province, People’s Republic of China (10JJ7003), the Free Exploration Program of Central South University of China (Nos. 201012200017,2011QNZT138) and the Graduate Innovation Foundation of Central South University of China (No. 2010ssxt048).

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