MiR-1281, a p53-responsive microRNA, impairs the survival of human osteosarcoma cells upon ER stress via targeting USP39.

MicroRNAs (miRNAs) are small regulatory non-coding RNAs that have been reported to play an important role in a variety of cellular functions. Recent studies indicated that some miRNAs are involved in regulating endoplasmic reticulum (ER) stress adaptation. However, the miRNAs were still unknown in osteosarcoma. In this study, we demonstrated that miR-1281 induced by ER stress promoted cell apoptosis and decreased ER stress adaptation of osteosarcoma in vitro and in vivo. Further mechanistic studies revealed that p53, an important tumor suppressor, directly bound to the promoter of miR-1281, leading to its increase under ER stress. Additionally, our data suggest that USP39 was the target of miR-1281 and participated in ER stress-induced cell apoptosis. Thus, our findings suggest a new role for miR-1281 in osteosarcoma and suggest that the p53-dependent, miR-1281-mediated USP39 pathway inhibits the survival of human osteosarcoma cells under ER stress.