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CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription
Epigenetic alterations have been functionally linked to ovarian cancer development and occurrence. The CXXC zinc finger protein 1 (CFP1) is an epigenetic regulator involved in DNA methylation and histone modification in mammalian cells. However, its role in ovarian cancer cells is unknown. Here, we...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9750859/ https://www.ncbi.nlm.nih.gov/pubmed/35864225 http://dx.doi.org/10.1038/s41417-022-00503-z |
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author | Yang, Liu-Qing Hu, Han-Yin Han, Yao Tang, Ze-Yi Gao, Jie Zhou, Qi-Yin Liu, Yi-Xuan Chen, Hao-Sa Xu, Tu-Nan Ao, Lei Xu, Ying Che, Xuan Jiang, Ya-Bo Xu, Chun-Wei Zhang, Xian-Chao Jiang, Yu-Xin Heger, Michal Wang, Xiao-Min Cheng, Shu-Qun Pan, Wei-Wei |
author_facet | Yang, Liu-Qing Hu, Han-Yin Han, Yao Tang, Ze-Yi Gao, Jie Zhou, Qi-Yin Liu, Yi-Xuan Chen, Hao-Sa Xu, Tu-Nan Ao, Lei Xu, Ying Che, Xuan Jiang, Ya-Bo Xu, Chun-Wei Zhang, Xian-Chao Jiang, Yu-Xin Heger, Michal Wang, Xiao-Min Cheng, Shu-Qun Pan, Wei-Wei |
author_sort | Yang, Liu-Qing |
collection | PubMed |
description | Epigenetic alterations have been functionally linked to ovarian cancer development and occurrence. The CXXC zinc finger protein 1 (CFP1) is an epigenetic regulator involved in DNA methylation and histone modification in mammalian cells. However, its role in ovarian cancer cells is unknown. Here, we show that CFP1 protein is highly expressed in human ovarian cancer tissues. Loss of CFP1 inhibited the growth of human ovarian cancer cells, promoted apoptosis, and increased senescence. CFP1 knockdown resulted in reduced levels of SETD1 (a CFP1 partner) and histone H3 trimethylation at the fourth lysine residue (H3K4me3). RNA-sequencing revealed that deletion of CFP1 resulted in mRNA reduction of bone marrow stromal cell antigen 2 (BST2). Bioinformatics analysis and chromatin immunoprecipitation showed that CFP1 binds to the promoter of BST2 and regulates its transcription directly. Overexpression of BST2 rescued the growth inhibitory effect of CFP1 loss. Furthermore, depletion of cullin-RING ubiquitin ligases 4 (CRL4) components ROC1 or CUL4A had significantly inhibited the expression of CFP1 and BST2 similar to MLN4924 treatment that blocked cullin neddylation and inactivated CRL4s. In conclusion, CFP1 promotes ovarian cancer cell proliferation and apoptosis by regulating the transcription of BST2, and the expression of CFP1 was affected by CRL4 ubiquitin ligase complex. |
format | Online Article Text |
id | pubmed-9750859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-97508592022-12-16 CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription Yang, Liu-Qing Hu, Han-Yin Han, Yao Tang, Ze-Yi Gao, Jie Zhou, Qi-Yin Liu, Yi-Xuan Chen, Hao-Sa Xu, Tu-Nan Ao, Lei Xu, Ying Che, Xuan Jiang, Ya-Bo Xu, Chun-Wei Zhang, Xian-Chao Jiang, Yu-Xin Heger, Michal Wang, Xiao-Min Cheng, Shu-Qun Pan, Wei-Wei Cancer Gene Ther Article Epigenetic alterations have been functionally linked to ovarian cancer development and occurrence. The CXXC zinc finger protein 1 (CFP1) is an epigenetic regulator involved in DNA methylation and histone modification in mammalian cells. However, its role in ovarian cancer cells is unknown. Here, we show that CFP1 protein is highly expressed in human ovarian cancer tissues. Loss of CFP1 inhibited the growth of human ovarian cancer cells, promoted apoptosis, and increased senescence. CFP1 knockdown resulted in reduced levels of SETD1 (a CFP1 partner) and histone H3 trimethylation at the fourth lysine residue (H3K4me3). RNA-sequencing revealed that deletion of CFP1 resulted in mRNA reduction of bone marrow stromal cell antigen 2 (BST2). Bioinformatics analysis and chromatin immunoprecipitation showed that CFP1 binds to the promoter of BST2 and regulates its transcription directly. Overexpression of BST2 rescued the growth inhibitory effect of CFP1 loss. Furthermore, depletion of cullin-RING ubiquitin ligases 4 (CRL4) components ROC1 or CUL4A had significantly inhibited the expression of CFP1 and BST2 similar to MLN4924 treatment that blocked cullin neddylation and inactivated CRL4s. In conclusion, CFP1 promotes ovarian cancer cell proliferation and apoptosis by regulating the transcription of BST2, and the expression of CFP1 was affected by CRL4 ubiquitin ligase complex. Nature Publishing Group US 2022-07-21 2022 /pmc/articles/PMC9750859/ /pubmed/35864225 http://dx.doi.org/10.1038/s41417-022-00503-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Yang, Liu-Qing Hu, Han-Yin Han, Yao Tang, Ze-Yi Gao, Jie Zhou, Qi-Yin Liu, Yi-Xuan Chen, Hao-Sa Xu, Tu-Nan Ao, Lei Xu, Ying Che, Xuan Jiang, Ya-Bo Xu, Chun-Wei Zhang, Xian-Chao Jiang, Yu-Xin Heger, Michal Wang, Xiao-Min Cheng, Shu-Qun Pan, Wei-Wei CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription |
title | CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription |
title_full | CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription |
title_fullStr | CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription |
title_full_unstemmed | CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription |
title_short | CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription |
title_sort | cpg-binding protein cfp1 promotes ovarian cancer cell proliferation by regulating bst2 transcription |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9750859/ https://www.ncbi.nlm.nih.gov/pubmed/35864225 http://dx.doi.org/10.1038/s41417-022-00503-z |
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