FOXN3, also known as CHES1, belongs to the forkhead box (FOX) protein family and functions as a transcriptional repressor [2,5]. It is involved in multiple biological processes, such as cell cycle regulation, and is associated with various signaling pathways like NF-κB, Smad, and AKT/MDM2/p53. FOXN3 plays a crucial role in maintaining normal physiological functions and its dysregulation is linked to numerous diseases, including cancers and pulmonary disorders [1,2,3,9]. Genetic models, especially gene knockout models, have been instrumental in uncovering its functions.

In gene-related functional studies, genetic ablation of FOXN3 phosphorylation in mouse models shows strong resistance to MRSA-induced pulmonary inflammatory injury, indicating its role in the inflammatory response to pulmonary infection [1]. In another case, knockdown of liver Foxn3 expression in adult mice leads to decreased fasting glucose and increased Myc expression, suggesting its role in regulating liver glucose metabolism [4]. In addition, over-expression of FOXN3 in nude mice inoculated with ovarian cancer cells delays the growth of ovarian cancer cells in vivo, revealing its anti-tumor effect [3].

In conclusion, FOXN3 is a key transcriptional repressor involved in cell cycle regulation, inflammation, and metabolism. Studies using gene knockout mouse models have demonstrated its significance in pulmonary inflammatory injury, liver glucose metabolism, and tumor development. These findings provide valuable insights into the biological functions of FOXN3 and its potential as a therapeutic target for related diseases.

References:

1. Zhu, Xinxing, Huang, Beijia, Zhao, Fengting, Zhang, Chen, Lin, Juntang. . p38-mediated FOXN3 phosphorylation modulates lung inflammation and injury through the NF-κB signaling pathway. In Nucleic acids research, 51, 2195-2214. doi:10.1093/nar/gkad057. https://pubmed.ncbi.nlm.nih.gov/36794705/

2. Kong, Xiangyi, Zhai, Jie, Yan, Chengrui, Brown, James A L, Fang, Yi. 2019. Recent Advances in Understanding FOXN3 in Breast Cancer, and Other Malignancies. In Frontiers in oncology, 9, 234. doi:10.3389/fonc.2019.00234. https://pubmed.ncbi.nlm.nih.gov/31214487/

3. Yang, Hua, Li, Mingyu, Qi, Yue. 2023. FOXN3 inhibits the progression of ovarian cancer through negatively regulating the expression of RPS15A. In Human cell, 36, 1120-1134. doi:10.1007/s13577-023-00876-9. https://pubmed.ncbi.nlm.nih.gov/37016167/

4. Karanth, Santhosh, Chaurasia, Bhagirath, Bowman, Faith M, Summers, Scott A, Schlegel, Amnon. . FOXN3 controls liver glucose metabolism by regulating gluconeogenic substrate selection. In Physiological reports, 7, e14238. doi:10.14814/phy2.14238. https://pubmed.ncbi.nlm.nih.gov/31552709/

5. Katoh, Masuko, Katoh, Masaru. . Human FOX gene family (Review). In International journal of oncology, 25, 1495-500. doi:. https://pubmed.ncbi.nlm.nih.gov/15492844/