Abstract 830: ZFP14, a p53 target, suppresses tumor formation by regulating HOXA gene cluster expression

Abstract

Abstract KRAB containing zinc finger proteins form the largest class of mammalian transcription factors. However, the physiological or pathological functions of the majority of them are unknown. Here, we established ZFP14 as a p53 target gene that is induced upon genotoxic stress in a p53-dependent manner. To determine the function of ZFP14 in mouse and human cancer cell lines, we generated ZFP14-KO cells that showed increased senescence as well as reduced cell growth and migration. Moreover, we showed that ZFP14 negatively regulates p53, which was the cause of reduced oncogenic properties in ZFP14-KO cancer cells. Mechanistically, we found that ZFP14 modulates p53 protein stability by associating with and possibly enhancing MDM2/p53 complex integrity through its zinc finger domains. Interestingly, we found that lower expression of ZFP14 correlates with poor patient survival in multiple human cancers. Notably, in a similar fashion, mice deficient in ZFP14 were susceptible to spontaneous tumor formation, developed other abnormalities such as systemic inflammation and liver steatosis, which led to their shorter lifespan. Finally, we showed that ZFP14 regulates the expression of the HOXA gene cluster in mouse and humans, which we propose as a possible mechanism by which ZFP14 regulates tumorigenesis. Our findings suggest that ZFP14 is an important regulator of p53 and HOXA genes during inflammation and tumorigenesis. Citation Format: Shakur Mohibi, Jin Zhang, Mingyi Chen, Xinbin Chen. ZFP14, a p53 target, suppresses tumor formation by regulating HOXA gene cluster expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 830.