Aurkb-KO Mouse

Aurkb, also known as Aurora kinase B, is a component of the chromosomal passenger protein complex. It is essential for chromosome segregation during cell division, playing a critical role in mitosis, cell cycle checkpoint, and DNA damage response (DDR) [3]. It is involved in various pathways, such as the PI3K/AKT/mTOR pathway [1].

Functional studies using loss-of-function approaches, including in vitro experiments like siRNA-mediated knockdown, have shown that downregulation of Aurkb inhibits cell proliferation, migration, and invasion, and induces apoptosis and cell cycle arrest in multiple cancer types. For example, in hepatocellular carcinoma (HCC), Aurkb downregulation inhibited HCC cell functions and lung metastasis, and it interacted with DHX9 to promote HCC progression via the PI3K/AKT/mTOR pathway [1]. In bladder cancer, Aurkb knockdown suppressed cell proliferation, migration, invasion, and cell cycle progression, and induced senescence, and this was rescued by MAD2L2 overexpression, as Aurkb activates MAD2L2 to downregulate the p53 DDR pathway [2]. In gastric cancer, silencing Aurkb inhibited cell proliferation, promoted apoptosis, arrested the cell cycle in G2/M phase, and inhibited invasion and migration, likely by inhibiting VEGFA/Akt/mTOR and Wnt/β-catenin/Myc pathways [4].

In conclusion, Aurkb is crucial for normal mitotic processes, but its dysregulation plays a significant role in promoting the progression of multiple cancers, including HCC, bladder cancer, and gastric cancer. Loss-of-function experiments have been instrumental in revealing its oncogenic roles, providing potential therapeutic targets for these cancer types.

References:

1. Zhu, Guoqing, Luo, Laihui, He, Yongzhu, Hu, Zhigao, Shan, Renfeng. 2024. AURKB targets DHX9 to promote hepatocellular carcinoma progression via PI3K/AKT/mTOR pathway. In Molecular carcinogenesis, 63, 1814-1826. doi:10.1002/mc.23775. https://pubmed.ncbi.nlm.nih.gov/38874176/

2. Li, Linzhi, Jiang, Pengcheng, Hu, Weimin, Ning, Jinzhuo, Cheng, Fan. 2024. AURKB promotes bladder cancer progression by deregulating the p53 DNA damage response pathway via MAD2L2. In Journal of translational medicine, 22, 295. doi:10.1186/s12967-024-05099-6. https://pubmed.ncbi.nlm.nih.gov/38515112/

3. Marima, Rahaba, Hull, Rodney, Penny, Clement, Dlamini, Zodwa. 2021. Mitotic syndicates Aurora Kinase B (AURKB) and mitotic arrest deficient 2 like 2 (MAD2L2) in cohorts of DNA damage response (DDR) and tumorigenesis. In Mutation research. Reviews in mutation research, 787, 108376. doi:10.1016/j.mrrev.2021.108376. https://pubmed.ncbi.nlm.nih.gov/34083040/

4. Wang, Zhen, Yu, Zhu, Wang, Gong-He, Chen, Jun-Qiang, Tian, Lei. 2020. AURKB Promotes the Metastasis of Gastric Cancer, Possibly by Inducing EMT. In Cancer management and research, 12, 6947-6958. doi:10.2147/CMAR.S254250. https://pubmed.ncbi.nlm.nih.gov/32801915/