title: Hypermethylation of PRDM1/Blimp-1 promoter in extranodal NK/T-cell lymphoma, nasal type: an evidence of predominant role in its downregulation.
abstract: The loss of PRDM1 expression is common in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT), but the role of promoter methylation in silencing PRDM1 expression remains unclear. Hence, we performed pyrosequencing analysis to evaluate the promoter methylation of PRDM1 gene in vivo and in vitro, to analyze the association between methylation and its expression, and to assess cellular effects of PRDM1 reexpression. The promoter hypermethylation of PRDM1 gene was detected in 11 of 25 EN-NK/T-NT cases (44.0%) and NK92 and NKL cells. The promoter hypermethylation of PRDM1 was significantly correlated with PRDM1 expression in vivo and in vitro, predominantly contributing to the loss of PRDM1 expression compared with genetic deletion and aberrant expression of miR-223 in EN-NK/T-NT. PRDM1 expression was significantly restored by demethylation treatment, which induced cell proliferation suppression, cell cycle arrest, and apoptosis increase. We also found that PRDM1 reexpression could downregulate the expression of Ets-1, T-bet, granzyme B, and c-myc. Our findings demonstrated that the promoter hypermethylation of PRDM1 harbored a predominant role in the downregulation of PRDM1 expression, significantly affecting the biological behavior of tumor cells in EN-NK/T-NT.
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Nong
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Jumei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015415:Biomarkers; D045744:Cell Line, Tumor; D019175:DNA Methylation; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D054391:Lymphoma, Extranodal NK-T-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D000074462:Positive Regulatory Domain I-Binding Factor 1 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D035683:MicroRNAs; C087042:PRDM1 protein, human; D000077209:Decitabine; D000074462:Positive Regulatory Domain I-Binding Factor 1; D001374:Azacitidine
keywords: PRDM1; extranodal NK/T-cell lymphoma; nasal type; promoter methylation