ZFP64 transcriptionally activates PD-1 and CTLA-4 and plays an oncogenic role in esophageal cancer.

ABSTRACT

Anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) are promising therapies for esophageal cancer. Zinc finger protein 64 (ZFP64) is precited as a transcriptional factor for PD-1 and CTLA-4 and presents high expression in esophagus cancer by bioinformatics analysis. The present study was designed to validate these results and to further explore the role of ZFP64 in esophagus cancer tumorigenesis. An orthotopic xenograft mouse model was established. Effects of ZFP64 on tumor growth and weight were assessed. Immunohistochemical staining was performed to reveal the protein expression of ZFP64, PD-1, and CTLA-4. Gain-of-function assays were performed to evaluate the influences of ZFP64 on cancer cell malignant phenotypes. The results revealed that ZFP64 transcriptionally activates PD-1 and CTLA-4 to increase their expression. ZFP64 plays an oncogenic role in esophageal cancer by promoting cancer cell proliferation, migration, invasion, and repressing apoptosis. ZFP64 also promotes esophageal cancer xenograft tumor growth in mice. In conclusion, ZFP64 increases PD-1 and CTLA-4 expression by binding to their promoters and facilitates esophageal cancer tumorigenesis, indicating ZFP64 protein transcription factor as a potential antidrug target in esophageal cancer.