Cbx8-KO Mouse

Cbx8, a core component of canonical polycomb repressive complex 1, is a paralogous chromobox protein. Canonical targeting of Polycomb repressive complex 1 by Cbx8 helps repress developmental genes, mediated by its recognition of H3K27me3 to maintain a repressive transcriptional state. It is involved in multiple biological processes such as cell proliferation, differentiation, and cell cycle progression [1-10].

In various cancers, functional studies have shown the oncogenic role of Cbx8. In lung adenocarcinoma, knockdown of Cbx8 reduced cell proliferation and migration both in vitro and in mouse models, revealing its promotion of tumor growth and metastasis through transcriptional repression of CDKN2C and SCEL [1]. Similarly, in ovarian carcinoma, depletion of Cbx8 suppressed growth and metastasis in vivo, and it was found to cobind with SET to the promoter of SUSD2 to suppress its transcription [2]. In glioma, high Cbx8 expression promoted cell proliferation, invasion, and migration, and led to radiotherapy tolerance, while in vivo tumors with low Cbx8 expression were more sensitive to radiotherapy [3]. Also, in hepatocellular carcinoma, CBX8 silencing inhibited the aggressive phenotype of cancer cells, and in esophageal squamous cell carcinoma, CBX8 knockdown inhibited cell proliferation, colony formation, DNA repair and promoted apoptosis [4,5].

In conclusion, Cbx8 plays a crucial role in regulating cell-related biological processes, especially in tumorigenesis. Model-based research, particularly the use of knockdown or knockout models in various cancer studies, has revealed its oncogenic functions in promoting cancer cell growth, metastasis, and radiotherapy resistance. These findings suggest Cbx8 as a potential therapeutic target for multiple cancers.

References:

1. Chen, Hao, Su, Yijie, Yang, Lihong, Liu, Min, Xuan, Chenghao. 2023. CBX8 promotes lung adenocarcinoma growth and metastasis through transcriptional repression of CDKN2C and SCEL. In Journal of cellular physiology, 238, 2710-2723. doi:10.1002/jcp.31124. https://pubmed.ncbi.nlm.nih.gov/37733753/

2. Wu, Yanjie, Duan, Yang, Li, Xuanyuan, Xue, Fengxia, Xuan, Chenghao. . CBX8 Together with SET Facilitates Ovarian Carcinoma Growth and Metastasis by Suppressing the Transcription of SUSD2. In Molecular cancer research : MCR, 20, 1611-1622. doi:10.1158/1541-7786.MCR-22-0139. https://pubmed.ncbi.nlm.nih.gov/35894945/

3. Liu, Qiang, Li, Xianguo, Gao, Wenhong. . CBX8 Promotes Cell Proliferation and Metastasis and Leads to Radiotherapy Tolerance of Glioma Cells. In Turkish neurosurgery, 33, 46-52. doi:10.5137/1019-5149.JTN.35022-21.2. https://pubmed.ncbi.nlm.nih.gov/35713250/

4. Tang, Bo, Tian, Yu, Liao, Yong, Qiu, Xiaoqiang, He, Songqing. 2019. CBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma. In Cell death & disease, 10, 52. doi:10.1038/s41419-018-1288-0. https://pubmed.ncbi.nlm.nih.gov/30718464/

5. Zhang, Yixuan, Chen, Hui, Zhu, Hongcheng, Sun, Xinchen. 2019. CBX8 promotes tumorigenesis and confers radioresistance in esophageal squamous cell carcinoma cells through targeting APAF1. In Gene, 711, 143949. doi:10.1016/j.gene.2019.143949. https://pubmed.ncbi.nlm.nih.gov/31255735/