Cdkn3-KO Mouse

CDKN3, short for cyclin-dependent kinase inhibitor 3, is a dual-specificity protein tyrosine phosphatase. It is involved in important biological processes such as mitosis and cell cycle regulation. It may be associated with several signaling pathways including P53, PI3K-AKT, cell cycle checkpoints, mitotic spindle checkpoint, and chromosome maintenance [6,7]. Understanding CDKN3's function is crucial as it has implications for various biological functions and disease development, and genetic models can be valuable tools for its study.

CDKN3 has been found to be upregulated in multiple cancer types. In cervical cancer, its upregulation is associated with low survival, making it a potential target for therapy [1]. In bladder cancer, CDKN3 promotes proliferation, migration, and confers cisplatin resistance via LDHA-dependent glycolysis reprogramming [2]. In colorectal cancer, it is highly expressed, correlated with poor prognosis, and regulates cisplatin resistance through TIPE1 [3]. In pancreatic cancer, PSMD12 and GID2 interact with CDKN3, affecting its ubiquitination and stability, and facilitating cancer progression [4,8]. In esophageal cancer, CDKN3 promotes tumor progression and cisplatin resistance via RAD51 [5]. In renal cell carcinoma, ZNF677 suppresses cancer progression through transcriptional repression of CDKN3 [9]. In hepatocellular carcinoma, CDKN3 expression is negatively correlated with survival and regulates adriamycin sensitivity [10].

In conclusion, CDKN3 plays a significant role in the cell cycle and mitosis. Model-based research, especially in the context of cancer, has revealed its importance in promoting tumor progression and conferring chemoresistance in various cancers. Understanding CDKN3's functions through these models provides potential therapeutic targets for treating cancers where CDKN3 is aberrantly regulated.

References:

1. Berumen, Jaime, Espinosa, Ana María, Medina, Ingrid. 2014. Targeting CDKN3 in cervical cancer. In Expert opinion on therapeutic targets, 18, 1149-62. doi:10.1517/14728222.2014.941808. https://pubmed.ncbi.nlm.nih.gov/25152075/

2. Li, Mengxuan, Che, Nan, Jin, Yu, Li, Jinhua, Yang, Wanshan. 2022. CDKN3 Overcomes Bladder Cancer Cisplatin Resistance via LDHA-Dependent Glycolysis Reprogramming. In OncoTargets and therapy, 15, 299-311. doi:10.2147/OTT.S358008. https://pubmed.ncbi.nlm.nih.gov/35388272/

3. Li, W-H, Zhang, L, Wu, Y-H. . CDKN3 regulates cisplatin resistance to colorectal cancer through TIPE1. In European review for medical and pharmacological sciences, 24, 3614-3623. doi:10.26355/eurrev_202004_20823. https://pubmed.ncbi.nlm.nih.gov/32329836/

4. Ma, Jia, Zhou, Wenyang, Yuan, Yifeng, Wang, Baosheng, Meng, Xiangpeng. 2023. PSMD12 interacts with CDKN3 and facilitates pancreatic cancer progression. In Cancer gene therapy, 30, 1072-1083. doi:10.1038/s41417-023-00609-y. https://pubmed.ncbi.nlm.nih.gov/37037907/

5. Wang, Jiansong, Che, Wencheng, Wang, Weimin, Zhen, Tianchang, Jiang, Zhongmin. 2019. CDKN3 promotes tumor progression and confers cisplatin resistance via RAD51 in esophageal cancer. In Cancer management and research, 11, 3253-3264. doi:10.2147/CMAR.S193793. https://pubmed.ncbi.nlm.nih.gov/31114363/

6. Chen, Yingjun, Li, Dai, Sha, Kaihui, Zhang, Xuezhong, Liu, Tonggang. 2024. Human pan-cancer analysis of the predictive biomarker for the CDKN3. In European journal of medical research, 29, 272. doi:10.1186/s40001-024-01869-6. https://pubmed.ncbi.nlm.nih.gov/38720365/

7. Zhang, Chuanlong, Shen, Qian, Gao, Mengqi, Li, Junchen, Pang, Bo. 2024. The role of Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in promoting human tumors: Literature review and pan-cancer analysis. In Heliyon, 10, e26061. doi:10.1016/j.heliyon.2024.e26061. https://pubmed.ncbi.nlm.nih.gov/38380029/

8. Deng, Xin, Ma, Jia, Zhou, Wenyang, Wang, Baosheng, Meng, Xiangpeng. 2023. GID2 Interacts With CDKN3 and Regulates Pancreatic Cancer Growth and Apoptosis. In Laboratory investigation; a journal of technical methods and pathology, 103, 100122. doi:10.1016/j.labinv.2023.100122. https://pubmed.ncbi.nlm.nih.gov/36828188/

9. Li, Aolin, Cao, Congcong, Gan, Ying, Yao, Lin, Zhang, Qian. . ZNF677 suppresses renal cell carcinoma progression through N6-methyladenosine and transcriptional repression of CDKN3. In Clinical and translational medicine, 12, e906. doi:10.1002/ctm2.906. https://pubmed.ncbi.nlm.nih.gov/35678231/

10. Dai, Wei, Fang, Shuo, Cai, Guanhe, Liu, Xiaoguang, Li, Mingyi. . CDKN3 expression predicates poor prognosis and regulates adriamycin sensitivity in hepatocellular carcinoma in vitro. In The Journal of international medical research, 48, 300060520936879. doi:10.1177/0300060520936879. https://pubmed.ncbi.nlm.nih.gov/32721244/