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

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

Journal: Cancer gene therapy 2022;29(12):1895-1907

PMID: 35864225

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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.

Address: Department of Cell Biology, College of Medicine, Jiaxing University, 118 Jiahang Road, Jiaxing, 314001, China.; Department of Anesthesiology, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children Hospital, Jiaxing University, Jiaxing, 314001, Zhejiang Province, China.; Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China.; Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, 350014, Fuzhou, Fujian, China.; Institute of Information Network and Artificial Intelligence, Jiaxing University, 118 Jiahang Road, Jiaxing, 314001, China.; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.; Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, the Netherlands.; Department of Cell Biology, College of Medicine, Jiaxing University, 118 Jiahang Road, Jiaxing, 314001, China. [email protected].; Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. [email protected].; G60 STI Valley Industry & Innovation Institute, Jiaxing University, 118 Jiahang Road, Jiaxing, 314001, China. [email protected].; Department of Cell Biology, College of Medicine, Jiaxing University, 118 Jiahang Road, Jiaxing, 314001, China. [email protected].; G60 STI Valley Industry & Innovation Institute, Jiaxing University, 118 Jiahang Road, Jiaxing, 314001, China. [email protected].

DOI: 10.1038/s41417-022-00503-z

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MeSH Terms: Female, Humans, Antigens, CD, Cell Proliferation, Cullin Proteins, GPI-Linked Proteins, Ovarian Neoplasms, Trans-Activators, Ubiquitins