文章：

CpG结合蛋白CFP1通过调控BST2转录促进卵巢癌细胞增殖

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

原文发布日期：2022-07-21 

英文摘要：

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. 

摘要翻译： 

表观遗传学改变与卵巢癌的发生发展存在功能性关联。CXXC锌指蛋白1（CFP1）是一种表观遗传调控因子，参与哺乳动物细胞中DNA甲基化和组蛋白修饰过程。然而，其在卵巢癌细胞中的作用尚未明确。本研究显示CFP1蛋白在人类卵巢癌组织中高表达。敲除CFP1可抑制卵巢癌细胞生长、促进细胞凋亡并加速衰老。CFP1 knockdown导致SETD1（CFP1结合蛋白）表达水平降低及组蛋白H3第四位赖氨酸三甲基化（H3K4me3）修饰减少。RNA测序分析发现CFP1缺失会引起骨髓基质细胞抗原2（BST2）的mRNA水平下降。生物信息学分析与染色质免疫沉淀实验表明，CFP1直接结合BST2启动子区域并调控其转录。过表达BST2可逆转CFP1缺失引起的生长抑制效应。此外，敲除cullin-RING泛素连接酶4（CRL4）组分ROC1或CUL4A后，CFP1与BST2的表达均受到显著抑制，该效应与MLN4924处理（通过阻断cullin蛋白的nedd化修饰使CRL4失活）结果一致。综上所述，CFP1通过调控BST2转录促进卵巢癌细胞增殖并抑制凋亡，且其表达受CRL4泛素连接酶复合体调控。

原文链接：

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