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Methylation-regulated ZNF545 inhibits growth of the p53-mutant KYSE150 cell line by inducing p21 and Bax

The Krüppel-associated box zinc-finger protein 545 (ZNF545) was recently identified as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). However, the role of ZNF545 in the tumorigenesis of esophageal cancer cells expressing loss-of-function mutant p53 has not been elucidated. In the p...

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Detalles Bibliográficos
Autores principales: Fan, Yu, Wang, Yu, Fu, Shaozhi, Liu, Duan, Lin, Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676145/
https://www.ncbi.nlm.nih.gov/pubmed/31410110
http://dx.doi.org/10.3892/etm.2019.7737
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author Fan, Yu
Wang, Yu
Fu, Shaozhi
Liu, Duan
Lin, Sheng
author_facet Fan, Yu
Wang, Yu
Fu, Shaozhi
Liu, Duan
Lin, Sheng
author_sort Fan, Yu
collection PubMed
description The Krüppel-associated box zinc-finger protein 545 (ZNF545) was recently identified as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). However, the role of ZNF545 in the tumorigenesis of esophageal cancer cells expressing loss-of-function mutant p53 has not been elucidated. In the present study, the role of ZNF545 in esophageal tumors and the p53-mutant ESCC cell line, KYSE150, was investigated. ZNF545 mRNA was significantly downregulated in tumors when compared with adjacent normal tissues. Methylated ZNF545 was detected in 76.6% of tumor tissues compared with 28.1% of adjacent normal tissues. Combined pharmacological treatment of KYSE150 cells with a demethylating reagent and deacetylase inhibitor restored the expression of ZNF545. Ectopic expression of ZNF545 activated p53 transcription and upregulated the protein expression levels of pivotal effectors p21 and Bax, which are associated with cell proliferation and apoptosis, respectively, in p53-mutant KYSE150 cells; while suppressing colony formation and inducing apoptosis. ZNF545 was therefore proposed as a potential tumor suppressor responsible for inhibiting the growth of p53-mutant ESCC cell lines. In addition, tumor-specific methylation of ZNF545 may represent an epigenetic diagnostic biomarker and a therapeutic target in patients with esophageal cancer.
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spelling pubmed-66761452019-08-13 Methylation-regulated ZNF545 inhibits growth of the p53-mutant KYSE150 cell line by inducing p21 and Bax Fan, Yu Wang, Yu Fu, Shaozhi Liu, Duan Lin, Sheng Exp Ther Med Articles The Krüppel-associated box zinc-finger protein 545 (ZNF545) was recently identified as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). However, the role of ZNF545 in the tumorigenesis of esophageal cancer cells expressing loss-of-function mutant p53 has not been elucidated. In the present study, the role of ZNF545 in esophageal tumors and the p53-mutant ESCC cell line, KYSE150, was investigated. ZNF545 mRNA was significantly downregulated in tumors when compared with adjacent normal tissues. Methylated ZNF545 was detected in 76.6% of tumor tissues compared with 28.1% of adjacent normal tissues. Combined pharmacological treatment of KYSE150 cells with a demethylating reagent and deacetylase inhibitor restored the expression of ZNF545. Ectopic expression of ZNF545 activated p53 transcription and upregulated the protein expression levels of pivotal effectors p21 and Bax, which are associated with cell proliferation and apoptosis, respectively, in p53-mutant KYSE150 cells; while suppressing colony formation and inducing apoptosis. ZNF545 was therefore proposed as a potential tumor suppressor responsible for inhibiting the growth of p53-mutant ESCC cell lines. In addition, tumor-specific methylation of ZNF545 may represent an epigenetic diagnostic biomarker and a therapeutic target in patients with esophageal cancer. D.A. Spandidos 2019-09 2019-07-05 /pmc/articles/PMC6676145/ /pubmed/31410110 http://dx.doi.org/10.3892/etm.2019.7737 Text en Copyright: © Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Fan, Yu
Wang, Yu
Fu, Shaozhi
Liu, Duan
Lin, Sheng
Methylation-regulated ZNF545 inhibits growth of the p53-mutant KYSE150 cell line by inducing p21 and Bax
title Methylation-regulated ZNF545 inhibits growth of the p53-mutant KYSE150 cell line by inducing p21 and Bax
title_full Methylation-regulated ZNF545 inhibits growth of the p53-mutant KYSE150 cell line by inducing p21 and Bax
title_fullStr Methylation-regulated ZNF545 inhibits growth of the p53-mutant KYSE150 cell line by inducing p21 and Bax
title_full_unstemmed Methylation-regulated ZNF545 inhibits growth of the p53-mutant KYSE150 cell line by inducing p21 and Bax
title_short Methylation-regulated ZNF545 inhibits growth of the p53-mutant KYSE150 cell line by inducing p21 and Bax
title_sort methylation-regulated znf545 inhibits growth of the p53-mutant kyse150 cell line by inducing p21 and bax
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676145/
https://www.ncbi.nlm.nih.gov/pubmed/31410110
http://dx.doi.org/10.3892/etm.2019.7737
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