ZFP161 promotes colorectal cancer progression by transcriptionally activating c-MYC

Zinc Finger Protein 161 (ZFP161) is a key regulator of Ataxia Telangiectasia and Rad3-related (ATR) signaling, playing a crucial role in maintaining genomic stability. Human ZFP161 activates <i>c-MYC</i>, whereas its murine ortholog, ZF5, serves as a putative transcriptional repressor of <i>c-MYC</i>. In this study, we identified ZFP161 as a direct regulator of c-MYC. We show that ZFP161 binds to the promoter region of <i>c-MYC</i>, modulating its expression and downstream signaling pathways. Additionally, ZFP161 promotes cell proliferation and tumorigenesis through c-MYC regulation and contributes to the malignant transformation of non-cancerous retinal pigment epithelial (RPE-1) cells. Furthermore, high <i>ZFP161</i> expression is associated with poor survival in patients with mixed colon adenocarcinoma. These findings suggest that the regulation of <i>c-MYC</i> by ZFP161 may represent a potential therapeutic target in <i>c-MYC</i>-driven cancers.