Selenos, also known as selenoprotein S, is a small, intrinsically disordered membrane protein. It is mainly known for its role in the ER-associated degradation (ERAD) pathway, which is responsible for extracting misfolded proteins from the endoplasmic reticulum (ER) to the cytosol for proteasomal degradation. Selenos is also involved in various cellular functions like inflammatory processes, cellular stress response, protein quality control, and signaling pathways. Genetic polymorphisms of Selenos are associated with increased risk for diabetes, dyslipidemia, and cardiovascular diseases, and its high expression levels correlate with poor prognosis in several cancers [2].

In yellow catfish, dietary inorganic Se induced lipogenesis via the HSF1-Selenos pathway, which up-regulated PPARγ expression. Blocking Selenos by RNA interference demonstrated its critical role in Se-induced lipid accumulation [1]. In colorectal cancer cells, knocking down Selenos sensitized ROS-mediated anti-tumor effects of regorafenib, as regorafenib promoted ROS production by suppressing Selenos expression. The combined treatment of regorafenib and oxaliplatin synergistically enhanced anti-tumor activities by activating ROS-mediated ER stress, JNK and p38 signaling pathways [3]. In triple-negative breast cancer, the combined overexpression of Selenos and valosin-containing protein (VCP/p97) correlated with advanced stages and poor prognosis [4].

In conclusion, Selenos plays important roles in lipid metabolism, oxidative stress-related anti-tumor effects, and cancer prognosis. Functional studies, especially those using loss-of-function approaches like RNA interference, have revealed its significance in these biological processes and disease conditions, providing insights into potential therapeutic strategies for related diseases.