The Deubiquitinase Yod1 Suppresses Tumor Progression By Stabilizing Znf24 In Clear Cell Renal Carcinoma Ji Liu Ying Lu Runye Zhu Ping Xi Zhihao Yang Zhipeng Zhang Yunbing Xiong Yifu Liu Qiqi Zhu Ting Sun Wenjie Xie Binbin Gong by Ji Liu & Ying Lu & Runye Zhu & Ping Xi & Zhihao Yang & Zhipeng Zhang & Yunbing Xiong & Yifu Liu & Qiqi Zhu & Ting Sun & Wenjie Xie & Binbin Gong 101038/S41419025076732 instant download after payment.

Metastasis remains a significant challenge in the management of clear cell renal cell carcinoma (ccRCC), and a continued focus onits underlying mechanisms is crucial for improving patient outcomes and optimizing clinical therapies. The ovarian-tumor relatedprotease (OTU) is involved in regulating critical cell signaling pathways, but the functions of most OTUs have yet to be explored. Inthis study, an unbiased RNAi screening revealed that ovarian tumor domain-containing 2 (YOD1) knockdown significantlypromoted cell metastasis. YOD1 downregulation promoted ccRCC growth and metastasis both in vitro and in vivo. Notably, YOD1knockdown stimulated the growth of organoids derived from ccRCC patients. Further investigation revealed that YOD1 directlyinteracted with and stabilized Zinc finger protein 24 (ZNF24) expression by deubiquitination in a manner dependent on its catalytic1234567890();,:activity. YOD1 inhibition attenuated ZNF24 transcriptional repression of vascular endothelial growth factor A (VEGFA), therebypromoting VEGFA gene expression. Furthermore, ZNF24 was identified as a key mediator of YOD1 function. The expression of YOD1and ZNF24 was significantly downregulated in tumor tissues, with a strong correlation between them. Importantly, reduced YOD1and ZNF24 levels were strongly associated with poor clinical outcomes in ccRCC patients. Our results reveal the mechanism bywhich YOD1 regulates VEGFA transcription and suppresses tumorigenesis by deubiquitinating ZNF24, providing a therapeutictarget in ccRCC.Cell Death and Disease (2025) 16:334 ;