Research note: Marek's disease oncogene Meq directly regulates CD30 high expression through binding to two regions in promoter.

Abstract

Marek's disease (MD), caused by the oncogenic Marek's disease virus (MDV), is a lymphoproliferative disease in chickens and serves as a natural animal model for CD30-overexpressing lymphomas. The expression of CD30, a member of the tumor necrosis factor receptor superfamily, is significantly upregulated during lymphocyte transformation in MD. The MDV-encoded proto-oncogene Meq is known to bind to the chicken CD30 promoter, but the precise regulatory mechanisms and functional binding sites remain uncharacterized. This study aimed to elucidate the transcriptional regulation of CD30 by Meq. Initially, expression of CD30 was detected in spleens of MDV-uninfected chickens and tumorous spleens of MDV-infected chickens, and the results showed it was highly expressed in tumorous spleens of MDV-infected chickens. Knockdown of Meq in vitro resulted in a corresponding downregulation of CD30 expression, confirming a positive regulatory relationship between them. Subsequently, dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP)-qPCR demonstrated that Meq directly bound to the CD30 promoter to activate its transcription, and the primary binding regions located at -1383 to -1162 bp and -97 to +75 bp relative to the transcription start site. Collectively, this study demonstrated Meq could bind to CD30 promoter at two binding regions and up-regulate its expression, and provided a critical foundation to investigate the role of the CD30 signaling pathway in MD-induced tumorigenesis.