CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription

Liu Qing Yang, Han Yin Hu, Yao Han, Ze Yi Tang, Jie Gao, Qi Yin Zhou, Yi Xuan Liu, Hao Sa Chen, Tu Nan Xu, Lei Ao, Ying Xu, Xuan Che, Ya Bo Jiang, Chun Wei Xu, Xian Chao Zhang, Yu Xin Jiang, Michal Heger, Xiao Min Wang*, Shu Qun Cheng, Wei Wei Pan

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Pages (from-to)1895-1907
Number of pages13
JournalCancer Gene Therapy
Volume29
Issue number12
DOIs
Publication statusPublished - Dec 2022

Bibliographical note

Funding Information:
This study was supported by The Natural Science Foundation of Zhejiang Province (LY21H160047, LY17H160060, Z20H160031, LGF20H160031, and Z20H160031), National Natural Science Foundation of China (31871402), National College Student Innovation and Entrepreneurship Training Program (202010354043, 202010354042, 2020R417015, 202110354015, 2021R417023, 202113291002, and 202113291003), Zhejiang Provincial Foreign Expert Grant (12.2018), a grant for the Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics (12.2019), the Dutch Cancer Foundation (KWF, project 10666), and the Top-level Talent Project of Zhejiang Province.

Publisher Copyright: © 2022, The Author(s).

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