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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-02-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347233/?tool=EBI |
| _version_ | 1797959082195288064 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T00:28:51Z |
| format | Article |
| id | doaj.art-d66e5be42da549b59418d04cb54b986c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T00:28:51Z |
| publishDate | 2011-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d66e5be42da549b59418d04cb54b986c2023-01-08T05:32:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-02-0162e1691610.1371/journal.pone.0016916ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer.Lihong GanShujie ChenJing ZhongXian WangEmily K Y LamXin LiuJianbin ZhangTianhua ZhouJun YuJianmin SiLiangjing WangHongchuan JinThe 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347233/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347233/?tool=EBI |
| work_keys_str_mv | AT lihonggan zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT shujiechen zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT jingzhong zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT xianwang zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT emilykylam zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT xinliu zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT jianbinzhang zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT tianhuazhou zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT junyu zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT jianminsi zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT liangjingwang zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer AT hongchuanjin zic1isdownregulatedthroughpromoterhypermethylationandfunctionsasatumorsuppressorgeneincolorectalcancer |