BMI1, also known as B cell-specific Moloney murine leukemia virus integration site-1, is a member of the PRC1 family and a transcriptional suppressor. It can maintain the self-renewal and proliferation of tissue-specific stem cells. BMI1 is involved in multiple cellular processes such as cell cycle progression, senescence, apoptosis, and angiogenesis [1,4].

BMI1 has been extensively studied in various diseases. In cancer, it is highly expressed in numerous malignancies like endometrial, hepatocellular, and breast cancers, promoting tumorigenesis through pathways such as the INK4a/ARF locus, NF-κB, and PTEN/PI3K/AKT [2,3,6]. In multiple myeloma, BMI1-KO MM-Φs (macrophages) from BM cells of BMI1-KO mice showed reduced proliferation, suppressed angiogenic factor expression, and lost the ability to protect MM cells from chemotherapy-induced cell death, indicating that BMI1 mediates the pro-myeloma functions of MM-Φs [5]. In spermatogonial stem cells, BMI1-deficient SSCs showed transcriptional activation of Wnt10b and nuclear translocation of β-catenin, and restoring Wnt/β-catenin signaling could rescue SSC maintenance, revealing a role of BMI1 in SSC maintenance [7].

In conclusion, BMI1 is crucial for maintaining the self-renewal and proliferation of tissue-specific stem cells and is involved in various disease processes. Studies using KO mouse models have significantly advanced our understanding of its role in cancer, multiple myeloma, and spermatogenesis, providing potential therapeutic targets for related diseases.

References:

1. Yang, Dan, Liu, Han-Qing, Yang, Zheng, Fan, Di, Tang, Qi-Zhu. 2021. BMI1 in the heart: Novel functions beyond tumorigenesis. In EBioMedicine, 63, 103193. doi:10.1016/j.ebiom.2020.103193. https://pubmed.ncbi.nlm.nih.gov/33421944/

2. Zhao, Yiting, Yang, Weili, Zheng, Kaifeng, Chen, Jun, Jin, Xiaofeng. 2022. The role of BMI1 in endometrial cancer and other cancers. In Gene, 856, 147129. doi:10.1016/j.gene.2022.147129. https://pubmed.ncbi.nlm.nih.gov/36563713/

3. Wang, Ru, Fan, Hengwei, Sun, Ming, Lv, Zhongwei, Yi, Wanwan. . Roles of BMI1 in the Initiation, Progression, and Treatment of Hepatocellular Carcinoma. In Technology in cancer research & treatment, 21, 15330338211070689. doi:10.1177/15330338211070689. https://pubmed.ncbi.nlm.nih.gov/35072573/

4. Sahasrabuddhe, Anagh A. 2016. BMI1: A Biomarker of Hematologic Malignancies. In Biomarkers in cancer, 8, 65-75. doi:10.4137/BIC.S33376. https://pubmed.ncbi.nlm.nih.gov/27168727/

5. Zhang, Danfeng, Huang, Jingcao, Wang, Fangfang, Niu, Ting, Zheng, Yuhuan. 2021. BMI1 regulates multiple myeloma-associated macrophage's pro-myeloma functions. In Cell death & disease, 12, 495. doi:10.1038/s41419-021-03748-y. https://pubmed.ncbi.nlm.nih.gov/33993198/

6. M, Janaki Ramaiah, S, Vaishnave. 2018. BMI1 and PTEN are key determinants of breast cancer therapy: A plausible therapeutic target in breast cancer. In Gene, 678, 302-311. doi:10.1016/j.gene.2018.08.022. https://pubmed.ncbi.nlm.nih.gov/30096458/

7. Yu, Jun, Shen, Cong, Lin, Meng, Zheng, Bo, Sun, Fei. 2022. BMI1 promotes spermatogonial stem cell maintenance by epigenetically repressing Wnt10b/β-catenin signaling. In International journal of biological sciences, 18, 2807-2820. doi:10.7150/ijbs.70441. https://pubmed.ncbi.nlm.nih.gov/35541907/