Identification and experimental validation of Stearoyl-CoA desaturase is a new drug therapeutic target for osteosarcoma

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor. Fatty acid reprogramming plays an essential role in OS progression. However, new fatty acid related therapeutic targets of OS have not been completely elucidated. Therefore, we firstly identified 113 differentially expressed fatty acid metabolism genes using bioinformatic analysis, 19 of which were found to be associated with OS prognosis. Then, 7 hub genes were screened out and yielded a strong prediction accuracy (AUC value = 0.88, at 3 years) for predicting the survival status of OS patients. Furthermore, we confirmed that SCD was highly expressed in OS cells and patients. And Knock-down of SCD impaired proliferation and migration of OS cells. Moreover, SCD was transcriptionally activated by c-Myc to promote proliferation and migration of OS cells. Finally, SCD inhibitor could significantly induce OS ferroptosis in vitro and in vivo. In conclusion, we identified that SCD was a reliable risk factor for OS patients. And SCD was activated by c-Myc. The inhibitor of SCD could significantly impaired OS growth and induce OS ferroptosis, which indicated that SCD was a potential drug target for OS treatment.