title: GALC gene is downregulated by promoter hypermethylation in Epstein-Barr virus-associated nasopharyngeal carcinoma.
abstract: The aim of the study was to investigate the tumor-suppressor effect of GALC in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) and determine whether GALC was downregulated by promoter hypermethy-lation in the NPC cell line, CNE-2Z. Forty-one archival NPC biopsy specimens were compared with 15 chronic nasopharyngitis specimens. EBV-encoded RNA (EBER) was verified by in situ hybridization and GALC protein expression was analyzed by immunohistochemistry. Promoter methylation in CNE-2Z cells was analyzed by bisulfite sequencing polymerase chain reaction. The functional role of GALC in NPC was investigated by restoring GALC expression in CNE-2Z cells via treatment with the DNA-deme-thylating agent 5-Aza-2'-deoxycytidine (5-Aza‑dC). EBER was expressed in 92.68% NPC specimens but no chronic nasopharyngitis specimens (P<0.01). GALC protein was present in 60% of chronic nasopharyngitis specimens and 24.39% NPC specimens (P<0.05). GALC protein expression was present significantly more frequently in tumors without lymph node metastasis than in those with metastasis (P<0.05). Logistic regression showed that GALC protein expression protected against lymph node metastasis (P<0.05). GALC protein expression was not correlated with age, gender and TNM stage (P>0.05). Treatment of GALC-negative CNE-2Z cells with 5-Aza-dC reduced GALC promoter methylation and restored GALC expression in a dose-dependent manner (P<0.05). The re-expression of GALC in CNE-2Z cells reduced cell proliferation and migration compared to the controls (P<0.05). GALC was downregulated by promoter hypermethylation and contributed to the pathogenesis of EBV-associated NPC. The findings showed the putative tumor-suppressor effect of GALC in NPC.
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Yinghai
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Zhijing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Zebin
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Pathophysiology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pathology, Gaozhou People's Hospital, Gaozhou, Guangdong 525200, P.R. China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Luo
authors.affiliation: Department of Physiology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Changli
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Jing
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Chen
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Prevention and Control, State Key Laboratory for Infectious Disease Prevention and Control, Beijing 100052, P.R. China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Du
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Prevention and Control, State Key Laboratory for Infectious Disease Prevention and Control, Beijing 100052, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D005698:Galactosylceramidase / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger
chemical_list: D012333:RNA, Messenger; D005698:Galactosylceramidase