ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.

The transcription factor, Zinc finger of the cerebellum (ZIC1), plays a crucial role in vertebrate development. Recently, ZIC1 has also been found to participate in the progression of human cancers, including medulloblastomas, endometrial cancers, and mesenchymal neoplasms. However, the function of...

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Autores principales:	Lihong Gan, Shujie Chen, Jing Zhong, Xian Wang, Emily K Y Lam, Xin Liu, Jianbin Zhang, Tianhua Zhou, Jun Yu, Jianmin Si, Liangjing Wang, Hongchuan Jin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d66e5be42da549b59418d04cb54b986c
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spelling	oai:doaj.org-article:d66e5be42da549b59418d04cb54b986c2021-11-18T06:58:47ZZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.1932-620310.1371/journal.pone.0016916https://doaj.org/article/d66e5be42da549b59418d04cb54b986c2011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347233/?tool=EBIhttps://doaj.org/toc/1932-6203The transcription factor, Zinc finger of the cerebellum (ZIC1), plays a crucial role in vertebrate development. Recently, ZIC1 has also been found to participate in the progression of human cancers, including medulloblastomas, endometrial cancers, and mesenchymal neoplasms. However, the function of ZIC1 in colon cancer progression has not been defined. In this study, we demonstrate ZIC1 to be silenced or significantly downregulated in colon cancer cell lines. These effects were reversed by demethylation treatment with 5-aza-2'-deoxycytidine (Aza). ZIC1 expression is also significantly downregulated in primary colorectal cancer tissues relative to adjacent non-tumor tissues (p = 0.0001). Furthermore, methylation of ZIC1 gene promoter is frequently detected in primary tumor tissues (85%, 34/40), but not in adjacent non-tumor tissues. Ectopic expression of ZIC1 suppresses cell proliferation and induces apoptosis, which is associated with MAPK and PI(3)K/Akt pathways, as well as the Bcl-xl/Bad/Caspase3 cascade. To identify target candidates of ZIC1, we employed cDNA microarray and found that 337 genes are downregulated and 95 genes upregulated by ectopic expression of ZIC1, which were verified by 10 selected gene expressions by qRT-PCR. Taken together, our results suggest that ZIC1 may potentially function as a tumor suppressor gene, which is downregulated through promoter hypermethylation in colorectal cancers.Lihong GanShujie ChenJing ZhongXian WangEmily K Y LamXin LiuJianbin ZhangTianhua ZhouJun YuJianmin SiLiangjing WangHongchuan JinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e16916 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lihong Gan Shujie Chen Jing Zhong Xian Wang Emily K Y Lam Xin Liu Jianbin Zhang Tianhua Zhou Jun Yu Jianmin Si Liangjing Wang Hongchuan Jin ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.
description	The transcription factor, Zinc finger of the cerebellum (ZIC1), plays a crucial role in vertebrate development. Recently, ZIC1 has also been found to participate in the progression of human cancers, including medulloblastomas, endometrial cancers, and mesenchymal neoplasms. However, the function of ZIC1 in colon cancer progression has not been defined. In this study, we demonstrate ZIC1 to be silenced or significantly downregulated in colon cancer cell lines. These effects were reversed by demethylation treatment with 5-aza-2'-deoxycytidine (Aza). ZIC1 expression is also significantly downregulated in primary colorectal cancer tissues relative to adjacent non-tumor tissues (p = 0.0001). Furthermore, methylation of ZIC1 gene promoter is frequently detected in primary tumor tissues (85%, 34/40), but not in adjacent non-tumor tissues. Ectopic expression of ZIC1 suppresses cell proliferation and induces apoptosis, which is associated with MAPK and PI(3)K/Akt pathways, as well as the Bcl-xl/Bad/Caspase3 cascade. To identify target candidates of ZIC1, we employed cDNA microarray and found that 337 genes are downregulated and 95 genes upregulated by ectopic expression of ZIC1, which were verified by 10 selected gene expressions by qRT-PCR. Taken together, our results suggest that ZIC1 may potentially function as a tumor suppressor gene, which is downregulated through promoter hypermethylation in colorectal cancers.
format	article
author	Lihong Gan Shujie Chen Jing Zhong Xian Wang Emily K Y Lam Xin Liu Jianbin Zhang Tianhua Zhou Jun Yu Jianmin Si Liangjing Wang Hongchuan Jin
author_facet	Lihong Gan Shujie Chen Jing Zhong Xian Wang Emily K Y Lam Xin Liu Jianbin Zhang Tianhua Zhou Jun Yu Jianmin Si Liangjing Wang Hongchuan Jin
author_sort	Lihong Gan
title	ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.
title_short	ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.
title_full	ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.
title_fullStr	ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.
title_full_unstemmed	ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.
title_sort	zic1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/d66e5be42da549b59418d04cb54b986c
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ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.

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