Selenoprotein S regulates tumorigenesis of clear cell renal cell carcinoma through AKT/ GSK3β/NF-κB signaling pathway

Clear cell renal cell carcinoma (ccRCC) is one of the most lethal genitourinary tumors with rapid progression and metastasis. Selenopmtein S (SELS), which is broadly expressed in human tissues, has been reported to be involved in ER homeostasis and inflammation. However, the biological roles of SELS in ccRCC remain unclear. In this study, we found that SELS expression was significantly higher in ccRCC and correlated with multiple dinicopathological features. Overexpression of SELS could promote cell proliferation and inhibit apoptosis in 786-0 cells, whereas silence of SELS elicited opposite effect. Further mechanistic studies revealed that SELS enhanced cell proliferation and inhibited apoptosis through activating AKT/GSK3 beta/NF-kappa B signaling pathway. Besides, SELS could stabilize c-Myc by preventing ubiquitin-proteasome-mediated degradation. Interestingly, we found that SELS could also inhibit migration of ccRCC cell likely through repressing epithelial-mesenchymal transition (EMT). Collectively, our findings suggested that SELS promoted tumor progression, and inhibited apoptosis and migration through AKT/GSK3 beta/NF-kappa B signaling pathway and EMT in ccRCC.

Automated summary

SELS is highly expressed in clear cell renal cell carcinoma (ccRCC) and associated with multiple pathological features. SELS overexpression promotes cell proliferation and inhibits apoptosis, while silence of SELS has the opposite effect. Mechanistically, SELS activates AKT/GSK3 beta/NF-kappa B signaling pathway to enhance cell proliferation and inhibit apoptosis, and stabilizes c-Myc by preventing ubiquitin-proteasome-mediated degradation. Furthermore, SELS inhibits ccRCC cell migration likely through repressing epithelial-mesenchymal transition (EMT).