Targeted DNA demethylation of the ZNF334 promoter inhibits colorectal cancer growth
Abstract Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Aberrant regulation of DNA methylation in promoters of tumor suppressor genes or proto-oncogenes is one of the fundamental processes driving the initiation and progression of CRC. Zinc-finger proteins (ZNFs) are one of t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05743-x |
| _version_ | 1797859823054749696 |
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| author | Bin Yang Haiyu Tang Nan Wang Jian Gu Qin Wang |
| author_facet | Bin Yang Haiyu Tang Nan Wang Jian Gu Qin Wang |
| author_sort | Bin Yang |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Aberrant regulation of DNA methylation in promoters of tumor suppressor genes or proto-oncogenes is one of the fundamental processes driving the initiation and progression of CRC. Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and function in many important biological processes related to tumorigenesis. Herein, we detected abnormal hypermethylation of the ZNF334 gene in CRC tissues compared with normal tissues, and this modification downregulated the expression of ZNF334. Furthermore, ten-eleven translocation 1 (TET1) was identified to be involved in regulating the methylation level of ZNF334. Next, a dCas9-multiGCN4/scFv-TET1CD-sgZNF334-targeted demethylation system was constructed to reverse the expression of ZNF334 through sgRNA targeting the ZNF334 promoter. Both in vitro and in vivo experiments demonstrated the targeted demethylation system upregulated ZNF334 expression and inhibited CRC growth. Collectively, targeted DNA demethylation of the ZNF334 promoter sheds light on the precise treatment of CRC. |
| first_indexed | 2024-04-09T21:35:50Z |
| format | Article |
| id | doaj.art-6f96578eb75741608a4139cc035b0905 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-09T21:35:50Z |
| publishDate | 2023-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-6f96578eb75741608a4139cc035b09052023-03-26T11:18:39ZengNature Publishing GroupCell Death and Disease2041-48892023-03-0114311010.1038/s41419-023-05743-xTargeted DNA demethylation of the ZNF334 promoter inhibits colorectal cancer growthBin Yang0Haiyu Tang1Nan Wang2Jian Gu3Qin Wang4School of Pharmacy, Southwest Minzu UniversitySchool of Pharmacy, Southwest Minzu UniversitySchool of Pharmacy, Southwest Minzu UniversitySchool of Pharmacy, Southwest Minzu UniversitySchool of Pharmacy, Southwest Minzu UniversityAbstract Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Aberrant regulation of DNA methylation in promoters of tumor suppressor genes or proto-oncogenes is one of the fundamental processes driving the initiation and progression of CRC. Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and function in many important biological processes related to tumorigenesis. Herein, we detected abnormal hypermethylation of the ZNF334 gene in CRC tissues compared with normal tissues, and this modification downregulated the expression of ZNF334. Furthermore, ten-eleven translocation 1 (TET1) was identified to be involved in regulating the methylation level of ZNF334. Next, a dCas9-multiGCN4/scFv-TET1CD-sgZNF334-targeted demethylation system was constructed to reverse the expression of ZNF334 through sgRNA targeting the ZNF334 promoter. Both in vitro and in vivo experiments demonstrated the targeted demethylation system upregulated ZNF334 expression and inhibited CRC growth. Collectively, targeted DNA demethylation of the ZNF334 promoter sheds light on the precise treatment of CRC.https://doi.org/10.1038/s41419-023-05743-x |
| spellingShingle | Bin Yang Haiyu Tang Nan Wang Jian Gu Qin Wang Targeted DNA demethylation of the ZNF334 promoter inhibits colorectal cancer growth Cell Death and Disease |
| title | Targeted DNA demethylation of the ZNF334 promoter inhibits colorectal cancer growth |
| title_full | Targeted DNA demethylation of the ZNF334 promoter inhibits colorectal cancer growth |
| title_fullStr | Targeted DNA demethylation of the ZNF334 promoter inhibits colorectal cancer growth |
| title_full_unstemmed | Targeted DNA demethylation of the ZNF334 promoter inhibits colorectal cancer growth |
| title_short | Targeted DNA demethylation of the ZNF334 promoter inhibits colorectal cancer growth |
| title_sort | targeted dna demethylation of the znf334 promoter inhibits colorectal cancer growth |
| url | https://doi.org/10.1038/s41419-023-05743-x |
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