Epigenetic regulation of human WIF1 and DNA methylation situation of WIF1 and GSTM5 in urothelial carcinoma
WNT inhibitory factor 1 (WIF1) is known to function as a tumor suppressor gene; it inhibits oncogene activation by preventing WNT signaling. This study investigated the epigenetic regulation of WIF1 gene in bladder cancer. We observed a positive relationship between WIF1 mRNA expression and survival...
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Elsevier
2023-05-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023032115 |
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| author | Cheng-Huang Shen Pei-Yu Li Shou-Chieh Wang Sin-Rong Wu Chih-Yu Hsieh Yuan-Chang Dai Yi-Wen Liu |
| author_facet | Cheng-Huang Shen Pei-Yu Li Shou-Chieh Wang Sin-Rong Wu Chih-Yu Hsieh Yuan-Chang Dai Yi-Wen Liu |
| author_sort | Cheng-Huang Shen |
| collection | DOAJ |
| description | WNT inhibitory factor 1 (WIF1) is known to function as a tumor suppressor gene; it inhibits oncogene activation by preventing WNT signaling. This study investigated the epigenetic regulation of WIF1 gene in bladder cancer. We observed a positive relationship between WIF1 mRNA expression and survival probability of bladder cancer patients. The WIF1 gene expression could be enhanced by DNA demethylation drug 5-aza-2′-deoxycytidine (5-aza-dC) and histone deacetylase inhibitor trichostatin A (TSA), suggesting that epigenetic modifications could regulate WIF1 gene expression. Overexpression of WIF1 inhibited cell proliferation and migration in 5637 cells, confirming the tumor suppressor role of WIF1. 5-Aza-dC dose dependently increased WIF1 gene expression while reducing DNA methylation level, suggesting that reversing WIF1 DNA methylation could activate its gene expression. We collected the cancer tissues and urine pellets of bladder cancer patients and only urine pellets from non-bladder cancer volunteers for DNA methylation analysis, but the methylation level of WIF1 gene −184 to +29 did not differ between patients and controls. We also analyzed glutathione S-transferase Mu 5 (GSTM5) gene methylation level because GSTM5 DNA hypermethylation was suggested to be a tumor biomarker in our previous study. It confirmed a higher GSTM5 DNA methylation in bladder cancer patients than in controls. In summary, this study suggests that the 5-aza-dC activated WIF1 gene which showed an anti-cancer effect, while WIF1 promoter −184 to +29 did not provide a suitable methylation assay region in clinical samples. In contrast, GSTM5 promoter −258 to −89 is a useful region for DNA methylation assay because it shows a higher methylation level in bladder cancer patients. |
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| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-13T08:25:04Z |
| publishDate | 2023-05-01 |
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| spelling | doaj.art-9e6c94feb5b84c34bf61d862ed40db542023-05-31T04:46:17ZengElsevierHeliyon2405-84402023-05-0195e16004Epigenetic regulation of human WIF1 and DNA methylation situation of WIF1 and GSTM5 in urothelial carcinomaCheng-Huang Shen0Pei-Yu Li1Shou-Chieh Wang2Sin-Rong Wu3Chih-Yu Hsieh4Yuan-Chang Dai5Yi-Wen Liu6Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, 600, Taiwan; SKBIO Technology Corporation, Taipei, 114065, TaiwanDepartment of Laboratory Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan; Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi City, TaiwanDivision of Nephrology, Department of Internal Medicine, Kuang Tien General Hospital, Taichung, 437, TaiwanDepartment of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi City, TaiwanDepartment of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi City, TaiwanDepartment of Laboratory Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan; Department of Pathology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, TaiwanDepartment of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi City, Taiwan; Corresponding author.WNT inhibitory factor 1 (WIF1) is known to function as a tumor suppressor gene; it inhibits oncogene activation by preventing WNT signaling. This study investigated the epigenetic regulation of WIF1 gene in bladder cancer. We observed a positive relationship between WIF1 mRNA expression and survival probability of bladder cancer patients. The WIF1 gene expression could be enhanced by DNA demethylation drug 5-aza-2′-deoxycytidine (5-aza-dC) and histone deacetylase inhibitor trichostatin A (TSA), suggesting that epigenetic modifications could regulate WIF1 gene expression. Overexpression of WIF1 inhibited cell proliferation and migration in 5637 cells, confirming the tumor suppressor role of WIF1. 5-Aza-dC dose dependently increased WIF1 gene expression while reducing DNA methylation level, suggesting that reversing WIF1 DNA methylation could activate its gene expression. We collected the cancer tissues and urine pellets of bladder cancer patients and only urine pellets from non-bladder cancer volunteers for DNA methylation analysis, but the methylation level of WIF1 gene −184 to +29 did not differ between patients and controls. We also analyzed glutathione S-transferase Mu 5 (GSTM5) gene methylation level because GSTM5 DNA hypermethylation was suggested to be a tumor biomarker in our previous study. It confirmed a higher GSTM5 DNA methylation in bladder cancer patients than in controls. In summary, this study suggests that the 5-aza-dC activated WIF1 gene which showed an anti-cancer effect, while WIF1 promoter −184 to +29 did not provide a suitable methylation assay region in clinical samples. In contrast, GSTM5 promoter −258 to −89 is a useful region for DNA methylation assay because it shows a higher methylation level in bladder cancer patients.http://www.sciencedirect.com/science/article/pii/S2405844023032115WNT inhibitory factor 1 (WIF1)Epigenetic regulationBladder cancerDNA promoter hypermethylationTumor biomarker |
| spellingShingle | Cheng-Huang Shen Pei-Yu Li Shou-Chieh Wang Sin-Rong Wu Chih-Yu Hsieh Yuan-Chang Dai Yi-Wen Liu Epigenetic regulation of human WIF1 and DNA methylation situation of WIF1 and GSTM5 in urothelial carcinoma Heliyon WNT inhibitory factor 1 (WIF1) Epigenetic regulation Bladder cancer DNA promoter hypermethylation Tumor biomarker |
| title | Epigenetic regulation of human WIF1 and DNA methylation situation of WIF1 and GSTM5 in urothelial carcinoma |
| title_full | Epigenetic regulation of human WIF1 and DNA methylation situation of WIF1 and GSTM5 in urothelial carcinoma |
| title_fullStr | Epigenetic regulation of human WIF1 and DNA methylation situation of WIF1 and GSTM5 in urothelial carcinoma |
| title_full_unstemmed | Epigenetic regulation of human WIF1 and DNA methylation situation of WIF1 and GSTM5 in urothelial carcinoma |
| title_short | Epigenetic regulation of human WIF1 and DNA methylation situation of WIF1 and GSTM5 in urothelial carcinoma |
| title_sort | epigenetic regulation of human wif1 and dna methylation situation of wif1 and gstm5 in urothelial carcinoma |
| topic | WNT inhibitory factor 1 (WIF1) Epigenetic regulation Bladder cancer DNA promoter hypermethylation Tumor biomarker |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023032115 |
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