Tumor antigen PRAME is up-regulated by MZF1 in cooperation with DNA hypomethylation in melanoma cells. (10th September 2017)

• Record Type: Journal Article
• Authors: Lee, Yong-Kyu; Park, Ui-Hyun; Kim, Eun-Joo; Hwang, Jin-Taek; Jeong, Ji-Cheon; Um, Soo-Jong
• Is Part Of: Cancer letters. Volume 403(2017)
• Page Start: 144
• Page End: 151
• Publication Date: 2017-09-10
• Subjects: PRAME -- MZF1 -- DNA methylation -- Gene expression -- Melanoma; PRAME preferentially expressed antigen in melanoma -- MZF1 myeloid zinc finger 1 -- 5-azaC 5-aza-2′-deoxycitidine -- siRNA small interfering RNA -- RT-qPCR reverse transcription-quantitative polymerase chain reaction -- ChIP Chromatin immunoprecipitation -- MeDIP Methylated DNA immunoprecipitation; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.06.015
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Elevated expression of preferentially expressed antigen in melanoma (PRAME) has been implicated in disease progression in a variety of cancers. However, the mechanisms underlying the transcriptional regulation of PRAME remain largely unexplored. Initially, we observed that PRAME was elevated in proportion to the malignant potential of melanoma cells. From the in silico prediction of PRAME gene structure, we identified the putative myeloid zinc finger 1 (MZF1) binding sites, which overlap with a CpG-rich region located in the first intron. The transcription factor MZF1 increased PRAME expression via its direct binding to the intron DNA. Upon treatment with a DNA methylation inhibitor, 5-aza-2′-deoxycitidine (5-azaC), together with ectopic expression of MZF1, PRAME expression was significantly enhanced at both the protein and mRNA levels. More pronounced MZF1 binding to the PRAME DNA was observed in the presence of 5-azaC. DNA methylation was inversely correlated with PRAME expression in melanoma cells. Finally, we observed that MZF1, like PRAME, promotes the colony-forming ability in melanoma cells. Overall, our findings suggest that MZF1, via stimulation of PRAME expression, may be a potential prognostic and therapeutic target in melanoma. Highlights: MZF1 acts as a transcription factor for the activation of PRAME gene. DNA hypomethylation cooperates with MZF1 to increase PRAME expression. MZF1 preferentially binds to the response element undergoing hypomethylation. PRAME expression in melanoma cells is inversely correlated with DNA methylation. Like PRAME, MZF1 increases the colony-forming potential of melanoma cells.