Aurkb-KO Mouse

Aurkb, also known as Aurora kinase B, is a component of the chromosomal passenger protein complex. It plays a critical role in mitosis, regulating chromosome segregation, cell cycle checkpoint, and DNA damage response (DDR) [3]. It is also involved in normal physiological processes. In the context of cancer, it has emerged as an important carcinogenic factor [6].

Aurkb is significantly overexpressed in multiple cancers, such as hepatocellular carcinoma (HCC), bladder cancer, gastric cancer, and intrahepatic cholangiocarcinoma (ICC) [1,2,4,5]. In HCC, down-regulation of Aurkb inhibits cell proliferation, migration, invasion, induces apoptosis, and causes cell cycle arrest, and also inhibits lung metastasis. It interacts with DHX9 and promotes HCC progression through the PI3K/AKT/mTOR pathway [1]. In bladder cancer, knockdown of Aurkb suppresses cell proliferation, migration, invasion, and cell cycle progression, and induces senescence, and these effects can be rescued by MAD2L2 overexpression as Aurkb activates MAD2L2 to down-regulate the p53 DDR pathway [2]. In gastric cancer, silencing Aurkb inhibits cell proliferation, arrests the cell cycle in G2/M phase, and inhibits invasion and migration, potentially through inhibiting VEGFA/Akt/mTOR and Wnt/β-catenin/Myc pathways [4,7]. In ICC, Aurkb promotes cell proliferation, induces epithelial-mesenchymal transition (EMT), migration, and invasion, and in vivo promotes tumor growth and metastasis, regulating EMT-related genes via the PI3K/AKT signaling axis [5].

In conclusion, Aurkb is essential for mitosis and DDR. Its overexpression in various cancers promotes cancer progression, including cell proliferation, migration, invasion, and metastasis. Functional studies, especially those using loss-of-function approaches, have revealed its role in cancer-related biological processes, highlighting Aurkb as a potential therapeutic target in multiple cancer types [1,2,4,5,6,7].

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. Nie, Min, Wang, Yadong, Yu, Zenong, Liu, Ming, Zhao, Quan. 2020. AURKB promotes gastric cancer progression via activation of CCND1 expression. In Aging, 12, 1304-1321. doi:10.18632/aging.102684. https://pubmed.ncbi.nlm.nih.gov/31982864/

5. Ma, Peng, Hao, Ying, Wang, Wei, Yu, Kai-Huan, Wang, Wei-Xing. 2023. AURKB activates EMT through PI3K/AKT signaling axis to promote ICC progression. In Discover oncology, 14, 102. doi:10.1007/s12672-023-00707-1. https://pubmed.ncbi.nlm.nih.gov/37318676/

6. Wan, Bangbei, Huang, Yuan, Liu, Bo, Lu, Likui, Lv, Cai. 2019. AURKB: a promising biomarker in clear cell renal cell carcinoma. In PeerJ, 7, e7718. doi:10.7717/peerj.7718. https://pubmed.ncbi.nlm.nih.gov/31576249/

7. 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/