title: Protocadherin8 is a functional tumor suppressor frequently inactivated by promoter methylation in nasopharyngeal carcinoma.
abstract: Protocadherin8 (PCDH8), an integral membrane protein, was reported to be a tumor suppressor involved in tumorigenesis in cancers. We aimed to investigate the epigenetic inactivation of PCDH8 and its tumor-suppressor function in nasopharyngeal carcinoma (NPC). Frequent downregulation/silencing of PCDH8 was found in NPC cell lines using semiquantitative PCR. Promoter methylation of PCDH8 was observed in 100% (5/5) of cell lines and 85.3% (35/41) of primary tumors by methylation-specific PCR, but not in normal nasopharyngeal tissues. Treatment of NPC cells with 5-aza-2'-deoxycytidine and/or trichostatin A could restore PCDH8 expression. Ectopic expression of PCDH8 in silenced NPC cells significantly inhibited cell colony formation and cell migration. For the first time, our study demonstrates the epigenetic inactivation of PCDH8 by promoter methylation and its tumor-suppressive function in NPC. Thus, PCDH8 could be identified as a tumor suppressor in NPC.
authors.affiliation: Department of Otolaryngology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Quan
authors.initials: Q
authors.lastname: Zeng
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
authors.forename: Tingxiu
authors.initials: T
authors.lastname: Xiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Qian
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Suling
authors.initials: S
authors.lastname: Hong
authors.forename: Guohua
authors.initials: G
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000091363:Protocadherins; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014945:Wound Healing
chemical_list: D015820:Cadherins; D006877:Hydroxamic Acids; C115816:PCDH8 protein, human; D000091363:Protocadherins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine