title: Inactivation of parkin by promoter methylation correlated with lymph node metastasis and genomic instability in nasopharyngeal carcinoma.
abstract: This study aimed to investigate the inactivation of the parkin gene by promoter methylation and its relationship with genome instability in nasopharyngeal carcinoma. Parkin was considered as a tumor suppressor gene in various types of cancers. However, its role in nasopharyngeal carcinoma is unexplored. Genomic instabilities were detected in nasopharyngeal carcinoma tissues by the random amplified polymorphic DNA. The methylation-specific polymerase chain reaction, semi-quantitative reverse transcription polymerase chain reaction, and immunohistochemical analysis were used to detect methylation and mRNA and protein expression of parkin in 54 cases of nasopharyngeal carcinoma tissues and 16 cases of normal nasopharyngeal epithelia tissues, and in 5 nasopharyngeal carcinoma cell lines (CNE1, CNE2, TWO3, C666, and HONE1) and 1 normal nasopharyngeal epithelia cell line (NP69). mRNA expression of parkin in CNE1 and CNE2 was analyzed before and after methyltransferase inhibitor 5-aza-2-deoxycytidine treatment. The relationship between promoter methylation and mRNA expression, demethylation and mRNA expression, and mRNA and protein expression of the gene and clinical factors and genomic instabilities were analyzed. The mRNA and protein expression levels were significantly reduced in 54 cases of human nasopharyngeal carcinoma compared with 16 cases of normal nasopharyngeal epithelia. Parkin-methylated cases showed significantly lower mRNA and protein expression levels compared with unmethylated cases. After 5-aza-2-deoxycytidine treatment, parkin mRNA expression was restored in CNE1 and CNE2; 92.59% (50/54) of nasopharyngeal carcinoma demonstrated genomic instability. Parkin is frequently inactivated by promoter methylation, and its mRNA and protein expression correlate with lymph node metastasis and genomic instability. Parkin deficiency probably promotes tumorigenesis in nasopharyngeal carcinoma.
authors.affiliation: 1 Department of Otolaryngology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Ni
authors.affiliation: 1 Department of Otolaryngology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: 1 Department of Otolaryngology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: 1 Department of Otolaryngology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Yuan
authors.affiliation: 1 Department of Otolaryngology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cao
authors.affiliation: 2 Department of Otolaryngology, First Affiliated Hospital, Guangxi Medical University, Nanning, China.
authors.forename: Guangwu
authors.initials: G
authors.lastname: Huang
authors.affiliation: 1 Department of Otolaryngology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000235:genetics; D002277:Carcinoma; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: Genome instability; lymph node metastasis; nasopharyngeal carcinoma; parkin gene; promoter methylation