GID2 Interacts With CDKN3 and Regulates Pancreatic Cancer Growth and Apoptosis.

Xin Deng, Jia Ma, Wenyang Zhou, Yifeng Yuan, Baosheng Wang, Xiangpeng Meng

Laboratory investigation; a journal of technical methods and pathology 2023 Jun

filter terms:

Dysregulation of deubiquitinase or ubiquitinase-mediated protein expression contributes to various diseases, including cancer. In the present study, we identified GID2, a subunit of the glucose-induced degradation-deficient (GID) complex that functions as an E3 ubiquitin ligase, as a potential key candidate gene in pancreatic cancer (PC) progression. The functional role and potential mechanism of GID2 in PC progression were investigated. Integrated bioinformatics analysis was performed to identify differentially expressed genes in PC based on the Gene Expression Profiling Interactive Analysis data sets. We found that GID2 was upregulated in PC tissues and that a high level of GID2 expression in clinical PC samples was positively associated with tumor stage and poor survival. Functional assays elucidated that GID2 expression promoted cell growth in vitro and accelerated tumor growth in vivo. GID2 knockdown effectively attenuated the malignant behaviors of PC cells and tumor formation. Furthermore, the protein network that interacted with the GID2 protein was constructed based on the GeneMANIA website. Cyclin-dependent kinase inhibitor 3 (CDKN3), a cell cycle regulator, was identified as a potential target of the GID2 protein. We revealed that GID2 positively regulated CDKN3 expression and inhibited CDKN3 ubiquitination. Furthermore, CDKN3 downregulation reversed the promoting effects of GID2 on PC progression. Therefore, the present study demonstrated that GID2 might regulate PC progression by maintaining the stability of the CDKN3 protein. These findings highlight the potential roles of the GID2/CDKN3 axis as a potential therapeutic target in PC. Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.

Citation

Xin Deng, Jia Ma, Wenyang Zhou, Yifeng Yuan, Baosheng Wang, Xiangpeng Meng. GID2 Interacts With CDKN3 and Regulates Pancreatic Cancer Growth and Apoptosis. Laboratory investigation; a journal of technical methods and pathology. 2023 Jun;103(6):100122