CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription.
CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription.
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CpG结合蛋白CFP1通过调节BST2转录促进卵巢癌细胞增殖
DOI：
10.1038/s41417-022-00503-z
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发表时间：
2022-12
影响因子：
6.4
通讯作者：
Pan, Wei-Wei
中科院分区：
文献类型：
--
作者：
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
表观遗传改变在功能上与卵巢癌的发展和发生有关。CXXC锌指蛋白1 （CFP1）是一种表观遗传调控因子，参与哺乳动物细胞DNA甲基化和组蛋白修饰。然而，它在卵巢癌细胞中的作用尚不清楚。在这里，我们发现CFP1蛋白在人卵巢癌组织中高表达。CFP1的缺失抑制了人卵巢癌细胞的生长，促进了细胞凋亡，增加了衰老。CFP1敲低导致SETD1 （CFP1的伴侣）和组蛋白H3在第四个赖氨酸残基（H3K4me3）上的三甲基化水平降低。rna测序显示，CFP1的缺失导致骨髓基质细胞抗原2 (BST2) mRNA的减少。生物信息学分析和染色质免疫沉淀表明，CFP1结合BST2启动子并直接调控其转录。BST2的过表达挽救了CFP1缺失的生长抑制作用。此外，cullin- ring泛素连接酶4 （CRL4）成分ROC1或CUL4A的缺失显著抑制了CFP1和BST2的表达，类似于MLN4924处理阻断cullin类泛素化和灭活CRL4s。综上所述，CFP1通过调控BST2的转录促进卵巢癌细胞增殖和凋亡，并且CFP1的表达受CRL4泛素连接酶复合物的影响。
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.
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