An Artificial CTCF Peptide Triggers Efficient Therapeutic Efficacy in Ocular Melanoma

Autor: Xuyang Wen, Jiayan Fan, Renbing Jia, Huixue Wang, Shengfang Ge, Peiwei Chai, He Zhang, Xiaoyu Zhang, Xianqun Fan, Tianyi Ding
Rok vydání: 2020
Předmět:
Zdroj: Molecular Therapy: Oncolytics, Vol 18, Iss, Pp 317-325 (2020)
Molecular Therapy Oncolytics
ISSN: 2372-7705
Popis: Although CCCTC binding factor (CTCF) has been demonstrated to play a variety of often contradictory roles in tumorigenesis, little is known about its function in the tumorigenesis of ocular melanoma. Here, we generated two artificial CTCF peptides (Decoy-CTCFs) combining the zinc finger domain of wild-type CTCF and artificial marker region. This Decoy-CTCF retained the DNA binding region but lost the functional regions of wild-type CTCF. Transferring artificial CTCF into ocular melanoma cells suppressed proliferation and migration in the tumor cells, while no effect was observed in normal cells. Intriguingly, we first showed that decoy-CTCF inhibited tumorigenesis by preventing the histone acetyltransferase EP300 from binding to the promoter of SELL. Thus SELL was a novel oncogene in the tumorigenesis of ocular melanoma. These studies provide efficient decoy CTCF-based therapeutic concept in malignant ocular melanoma and reveal the potential mechanism underlying decoy-based tumor therapy.
Graphical Abstract
An artificial CTCF peptide (Decoy-CTCFs) prevents the histone acetyltransferase EP300 to interact the promoter of SELL for inactivating SELL expression and triggering efficient therapeutic efficacy in ocular tumors. These studies delineate a novel decoy CTCF-guided mechanism in tumor therapy and provide a promising therapeutic concept for ocular melanoma.
Databáze: OpenAIRE