title: NOR1 is an HSF1- and NRF1-regulated putative tumor suppressor inactivated by promoter hypermethylation in nasopharyngeal carcinoma.
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.
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Xiangya Road, Changsha, Hunan 410078, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.forename: Yixin
authors.initials: Y
authors.lastname: Tan
authors.forename: Mei
authors.initials: M
authors.lastname: Yi
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yang
authors.forename: James B
authors.initials: JB
authors.lastname: McCarthy
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Minghua
authors.initials: M
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.forename: Bo
authors.initials: B
authors.lastname: Su
authors.forename: Zuping
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Liao
authors.forename: Bo
authors.initials: B
authors.lastname: Xiang
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation; D000077209:Decitabine; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000209:etiology* / Q000235:genetics; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D026901:Membrane Transport Proteins; C479458:OSCP1 protein, human; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine