Oncogenic gene TRIM10 confers resistance to cisplatin in osteosarcoma cells and activates the NF-κB signaling pathway.

Abstract

Deregulation of tripartite motif (TRIM) family proteins contribute to multiple biological processes such as neurodegeneration, development, inflammation, cell survival, apoptosis, and carcinogenesis. However, the biological function and molecular mechanism of TRIM family proteins in osteosarcoma chemoresistance remain unclear. In the current study, we found the protein expression of TRIM10 was markedly overexpressed in cisplatin resistance's osteosarcoma tissues and TRIM10 overexpression was inversely correlated with osteosarcoma patient survival. Furthermore, overexpression of TRIM10 confers cisplatin resistance on osteosarcoma cells; however, repressing TRIM10 sensitized osteosarcoma cell lines to cisplatin cytotoxicity in vitro. Mechanically, TRIM10 upregulated the nuclear levels of p65, thereby activating canonical NF-κB signaling. Taken together, our results suggest that TRIM10 contributed to cisplatin resistance in osteosarcoma cells, and targeting the TRIM10/p65 axis may represent a promising strategy to enhance cisplatin response in osteosarcoma patients with chemoresistance.