title: Promoter methylation-mediated downregulation of PRDM5 contributes to the development of lung squamous cell carcinoma.
abstract: PRDM5 has been proposed as a tumor suppressor frequently downregualted in tumor. In this study, lung squamous cell carcinoma tissues and adjacent nontumorous normal tissues were collected from 30 patients. PRDM5 expression was detected by reverse transcription polymerase chain reaction and Western blot analysis, DNA methylation of PRDM5 promoter was analyzed by methylation-specific PCR. SK-MES-1 cells or xenografts in nude mice were treated with 5-aza-2'-deoxycitydine, and cell proliferation and tumor growth in nude mice were examined. We found that PRDM5 promoter was methylated and PRDM5 expression at both mRNA and protein levels was reduced in lung squamous cell carcinoma tissues. Furthermore, PRDM5 promoter methylation was significantly correlated with tumor differentiation and lymph node metastasis of lung squamous cell carcinoma, but not with age, gender, smoking, or tumor grade. 5-aza-2'-deoxycitydine inhibited the proliferation of SK-MES-1 cells and the growth of xenografts in nude mice, accompanied by reduced methylation of PRDM5 promoter and increased expression of PRDM5. Taken together, our data suggest that PRDM5 is a tumor suppressor in lung cancer and is a promising target for the diagnosis, prognosis, and therapy of lung squamous cell carcinoma.
authors.affiliation: Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.
authors.forename: Shuang-Xiang
authors.initials: SX
authors.lastname: Tan
authors.forename: Rui-Cheng
authors.initials: RC
authors.lastname: Hu
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Tan
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Liu
authors.forename: Wen-En
authors.initials: WE
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D000077209:Decitabine; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C487762:PRDM5 protein, human; D014157:Transcription Factors; D000077209:Decitabine; D001374:Azacitidine