MiR-383 sensitizes osteosarcoma cells to cisplatin treatment via down-regulating PSMB5

Abstract

Abstract Background： Proteasome inhibition represents a promising strategy for cancer therapy. Bortezomib, primarily targeting the chymotrypsin-like activity of PSMB5, has been proven effective in several tumors. However, variable sensitivity exits in response to bortezomib, which may be partially due to differences in the expression of proteasome subunits. Methods and Results: In this study, we investigated whether miR-383 affects the proteasome subunits expression in osteosarcoma (OS) cells, and if so, whether OS cells display differential sensitivity to bortezomib concerning miR-383 expression. We detected a decreased miR-383 expression in OS cells and tissues. Then we found a negative correlation between bortezomib cytotoxicity and proteasome 20S core particle subunit β5 (PSMB5) expression level. Intriguingly, we found that PSMB5 is a target of miR-383. Higher expression of miR-383 led to decreased PSMB5 expression and exhibited greater sensitivity to bortezomib in OS cells. Conclusions: In summary, our results represent the first comprehensive analysis of the role of miR-383 in OS. The results suggest that miR-383 may enhance the anticancer effect of bortezomib through PSMB5 repression, providing a novel therapeutic strategy in OS and a new pathway for proteasome regulation.