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

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.

Colocalization of Cancer Associated Biomarkers on Single Extracellular Vesicles for Early Cancer Detection

“…Bone marrow stromal antigen-2/CD317/Tetherin (BST2), Folate receptor alpha (FOLR1), and Mucin-1 (MUC1) are cell surface proteins previously shown to be overexpressed in ovarian cancer (Gautam et al, 2023; Giampaolino et al, 2020, 2019; Januchowski et al, 2017; Kufe, 2009; Trinidad et al, 2023; Varaganti et al, 2023; Yang et al, 2022). Protein expression of all three biomarkers was demonstrated by western blotting to be present in the EV fractions from human ovarian cancer cell lines (Figure 2) and human plasma (not shown) enriched by size exclusion.…”

Italian Precision Medicine in Pediatric Oncology: Moving beyond Actionable Alterations

“…The CXXC zinc finger protein 1 (CFP1) is an epigenetic regulator involved in DNA methylation and histone modification in mammalian cells. CFP1 promotes ovarian cancer cell proliferation and apoptosis, and the expression of CFP1 is reported to be affected by the CRL4 ubiquitin ligase complex [ 31 ]. Furthermore, cell cycle progression in mammals is modulated by two ubiquitin ligase complexes, CRL4 and SCF, which facilitate the degradation of chromatin substrates involved in the regulation of DNA replication.…”

Bone marrow stromal cell antigen 2: Tumor biology, signaling pathway and therapeutic targeting (Review)

“…An increasing number of studies have shown that BST2 upregulation is associated with numerous types of cancer, including endometrial cancer ( 10 ), glioblastoma multiforme ( 12 ), nasopharyngeal cancer ( 14 ), oral cavity cancer ( 15 ), OSCC ( 16 ), cervical cancer ( 17 ), pancreatic cancer ( 19 ), head and neck squamous cell carcinoma ( 23 ), ovarian cancer ( 24 ), esophageal squamous cell carcinoma ( 22 ) and bladder cancer ( 25 ).…”

“…Sixth, the transcription factor SP1 protein regulates the BST2 gene by binding to the BST2 promoter, and can promote cell proliferation and migration in pancreatic cancer ( 19 ). The CXXC zinc finger protein 1 can bind to the promoter of BST2 to directly regulate its transcription in ovarian cells ( 24 ). Seventh, the chemokine SDF1a interacts with CXCR4/CXCR7 to promote an invasive phenotype in the medullary thyroid by upregulating BST2 gene expression in thyroid cancer ( 98 ).…”

“…The BST2 gene is widely expressed in numerous cells, including hepatocytes, plasma blast cells, early plasma cells, mature B cells, dendritic cells, pneumocytes, monocytes, pancreatic cells, kidney cells and vascular endothelial cells, suggesting that it plays vital roles in the innate immune response against viral infection and other physiological processes ( 2 , 5 – 7 ). An increasing number of studies have shown that BST2 upregulation is associated with numerous types of cancer, such as multiple myeloma ( 8 , 9 ), endometrial cancer ( 10 ), gastric cancer ( 11 ), glioblastoma multiforme ( 12 ), primary lung cancer ( 13 ), nasopharyngeal cancer ( 14 ), oral cavity cancer ( 15 ), oral squamous cell carcinoma (OSCC) ( 16 ), cervical cancer ( 17 ), breast cancer ( 18 ), pancreatic cancer ( 19 ), hepatocellular carcinoma (HCC) ( 20 ), colorectal cancer ( 21 , 22 ), head and neck squamous cell carcinoma ( 23 ), ovarian cancer ( 24 ), esophageal squamous cell carcinoma ( 22 ) and bladder cancer ( 25 ). The role and molecular mechanism of high BST2 expression have been investigated in several types of cancer; however, a review of the molecular mechanism of BST2 in these cancers not been reported.…”