Selenos-KO Mouse

Selenos, also known as selenoprotein S, is a small, intrinsically disordered membrane protein. It is primarily known for its role in the ER-associated degradation (ERAD) pathway, which is crucial for extracting misfolded proteins from the endoplasmic reticulum (ER) for proteasomal degradation. Additionally, Selenos is involved in inflammatory processes, cellular stress response, protein quality control, and signaling pathways, playing a significant role in maintaining cellular homeostasis [2].

Selenos has been associated with various diseases. In yellow catfish, the HSF1-SELENOS pathway mediated dietary inorganic Se-induced lipogenesis via up-regulating PPARγ expression, suggesting its role in lipid metabolism [1]. In humans, its genetic polymorphisms are linked to an increased risk of diabetes, dyslipidemia, and cardiovascular diseases, while high expression levels correlate with poor prognosis in several cancers [2]. For example, in brain lower-grade glioma, SELENOS is a potential prognostic biomarker, and its low expression is associated with a favorable prognosis [3]. In stroke, genetically elevated SELENOS levels are associated with an increased risk of all-cause stroke, ischemic stroke, and intracerebral hemorrhage [4]. In colon cancer cells, regorafenib promotes ROS production by suppressing SELENOS, enhancing the anti-tumor effects of oxaliplatin [5]. In triple-negative breast cancer, the combined overexpression of SELENOS and VCP/p97 is related to advanced stages and poor prognosis [6].

In conclusion, Selenos is a versatile protein involved in multiple cellular functions and is associated with various diseases. Studies on Selenos, including those potentially using gene knockout or conditional knockout models (although not specifically detailed in the provided references), help in understanding its role in biological processes and disease conditions, providing potential insights for disease prevention and treatment.

References:

1. Zhang, Dian-Guang, Xu, Xiao-Jian, Pantopoulos, Kostas, Zheng, Hua, Luo, Zhi. 2022. HSF1-SELENOS pathway mediated dietary inorganic Se-induced lipogenesis via the up-regulation of PPARγ expression in yellow catfish. In Biochimica et biophysica acta. Gene regulatory mechanisms, 1865, 194802. doi:10.1016/j.bbagrm.2022.194802. https://pubmed.ncbi.nlm.nih.gov/35248747/

2. Ghelichkhani, Farid, Gonzalez, Fabio A, Kapitonova, Mariia A, Cheng, Rujin, Rozovsky, Sharon. 2022. Selenoprotein S: A versatile disordered protein. In Archives of biochemistry and biophysics, 731, 109427. doi:10.1016/j.abb.2022.109427. https://pubmed.ncbi.nlm.nih.gov/36241082/

3. Wang, Yuetong, Qu, Kai, Xia, Zengrun, Ke, Zunhua, Zhang, Rongqiang. 2024. Selenoprotein S (SELENOS) is a potential prognostic biomarker for brain lower grade glioma. In Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 86, 127539. doi:10.1016/j.jtemb.2024.127539. https://pubmed.ncbi.nlm.nih.gov/39378668/

4. He, Yan, Liu, Yi, Meng, Haoliang, Zhu, Zhengbao, Gao, Yuzhen. 2025. Genetically Elevated Selenoprotein S Levels and Risk of Stroke: A Two-Sample Mendelian Randomization Analysis. In International journal of molecular sciences, 26, . doi:10.3390/ijms26041652. https://pubmed.ncbi.nlm.nih.gov/40004116/

5. Yu, Yun, Wu, Tao, Zhang, Xiaodong, Li, Shaotang, Cui, Ri. 2023. Regorafenib activates oxidative stress by inhibiting SELENOS and potentiates oxaliplatin-induced cell death in colon cancer cells. In European journal of pharmacology, 957, 175986. doi:10.1016/j.ejphar.2023.175986. https://pubmed.ncbi.nlm.nih.gov/37598924/

6. Costantini, Susan, Polo, Andrea, Capone, Francesca, Ciliberto, Gennaro, Budillon, Alfredo. 2022. An Integrated In Silico, In Vitro and Tumor Tissues Study Identified Selenoprotein S (SELENOS) and Valosin-Containing Protein (VCP/p97) as Novel Potential Associated Prognostic Biomarkers in Triple Negative Breast Cancer. In Cancers, 14, . doi:10.3390/cancers14030646. https://pubmed.ncbi.nlm.nih.gov/35158912/