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Here, we have identified XPA as a novel target gene of EZH2 via a DNA repair pathway PCR array. XPA plays a pivot role in nucleotide excision repair (NER). The expression of XPA was significantly increased by EZH2 specific inhibitor GSK126 or lentiviral shEZH2 in nasopharyngeal carcinoma (NPC) CNE and 8F cell lines. Chromatin immunoprecipitation assay demonstrated that EZH2 catalyzes H3K27 trimethylation at the XPA promoters. Furthermore, we validated the negative correlation of EZH2 and XPA in a NPC tissue microarray by immunohistochemistry staining. We also found that high expression of EZH2 was positively correlated with advanced T, N, and AJCC stage of NPC; and low expression of XPA was positively correlated with advanced T and N stage. In NPC cell lines, increased XPA expression by EZH2 inhibition resulted in a more rapid removal of UVC induced 6\u20104PP\u2010 and CPD\u2010DNA adducts, as well as enhanced efficiency of DNA repair after UVC irradiation as detected by the Comet assay and immunofluorescence staining of \u03b3H2Ax. Consistently, increased cell clonogenic survival, decreased apoptosis, and necrosis after UVC irradiation, and increased resistance to DNA damaging agent cisplatin was also observed in EZH2 inhibited cells. These results illustrate that EZH2 may promote carcinogenesis and cancer development of NPC by transcriptional repression of XPA gene and inactivation of NER pathway. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22507","type":"journal-article","created":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T13:20:50Z","timestamp":1464873650000},"page":"447-463","source":"Crossref","is-referenced-by-count":12,"title":["EZH2 suppresses the nucleotide excision repair in nasopharyngeal carcinoma by silencing XPA gene"],"prefix":"10.1002","volume":"56","author":[{"given":"Yuxiang","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Fudan University Shanghai Cancer Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese Medicine and Western Medicine School of Medicine Yangzhou University 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