Bex1, or Brain Expressed X-linked protein 1, has diverse essential functions. It is involved in ciliogenesis, axon regeneration, and differentiation of neural stem cells [3,5]. Bex1 is associated with pathways such as Wnt/β-catenin, which is crucial for stemness maintenance in liver cancer [1]. Its overall biological importance lies in its roles in cell self-renewal, metabolism, and immune responses. Genetic models, especially knockout (KO) mouse models, have been valuable in studying Bex1.

In KO mouse models, Bex1-knockout mice showed lower axon regeneration capability after peripheral nerve injury compared to wild-type mice, indicating its role in axon regeneration [5]. In liver cancer, Bex1 was identified as a novel cancer stem cell (CSC) marker. DNMT1-mediated methylation of the Bex1 promoter led to differential expression patterns in different types of liver cancer. Bex1 interacted with RUNX3 to activate Wnt/β-catenin signaling, essential for self-renewal and maintenance of liver CSCs [1]. In hepatoblastoma (HB), Bex1 promoted stemness maintenance by facilitating the Warburg effect in a PPARγ/PDK1-dependent manner, and HB patients with high Bex1 and PDK1 expression had a poor prognosis [2]. In viral myocarditis, Bex1-knockout mice had accelerated coxsackievirus B3 (CVB3)-driven heart failure and pathologic heart remodeling, while transgenic mice overexpressing Bex1 counteracted viral replication in the heart, suggesting Bex1's role in the cardiac antiviral immune response [4].

In conclusion, Bex1 plays multifaceted roles in biological processes such as ciliogenesis, axon regeneration, and stemness maintenance. Its KO mouse models have revealed its significance in diseases like liver cancer, hepatoblastoma, and viral myocarditis. Understanding Bex1's functions helps in developing potential therapeutic strategies for these diseases.

References:

1. Wang, Qian, Liang, Ning, Yang, Tao, He, Xianli, Liu, Chaoxu. 2021. DNMT1-mediated methylation of BEX1 regulates stemness and tumorigenicity in liver cancer. In Journal of hepatology, 75, 1142-1153. doi:10.1016/j.jhep.2021.06.025. https://pubmed.ncbi.nlm.nih.gov/34217777/

2. Wang, Qian, Liang, Ning, Liu, Chaoxu, Yang, Tao, Wang, Gang. 2023. BEX1 supports the stemness of hepatoblastoma by facilitating Warburg effect in a PPARγ/PDK1 dependent manner. In British journal of cancer, 129, 1477-1489. doi:10.1038/s41416-023-02418-4. https://pubmed.ncbi.nlm.nih.gov/37715024/

3. Hibino, Emi, Ichiyama, Yusuke, Tsukamura, Atsushi, Nishimura, Masaki, Mori, Masaki. 2022. Bex1 is essential for ciliogenesis and harbours biomolecular condensate-forming capacity. In BMC biology, 20, 42. doi:10.1186/s12915-022-01246-x. https://pubmed.ncbi.nlm.nih.gov/35144600/

4. Martens, Colton R, Dorn, Lisa E, Kenney, Adam D, Yount, Jacob S, Accornero, Federica. 2022. BEX1 is a critical determinant of viral myocarditis. In PLoS pathogens, 18, e1010342. doi:10.1371/journal.ppat.1010342. https://pubmed.ncbi.nlm.nih.gov/35192678/

5. Khazaei, Mohammad R, Halfter, Hartmut, Karimzadeh, Fereshteh, Margolis, Frank L, Young, Peter. 2010. Bex1 is involved in the regeneration of axons after injury. In Journal of neurochemistry, 115, 910-20. doi:10.1111/j.1471-4159.2010.06960.x. https://pubmed.ncbi.nlm.nih.gov/20731761/