GLS1 Promotes The Malignant Progression of Osteosarcoma

Abstract Background: Osteosarcoma (OS) is the most frequent and high-grade young malignant bone tumor. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy and chemotherapy. Metabolic reprogramming currently is recognized as one of the hallmarks of cancer. Glutaminase 1(GLS1) has been associated with progression of tumor cell through CDK4 signaling pathway.Methods: In the study, Western blot was used to detect the expression of GLS1 protein in tumor and adjacent normal tissues of osteosarcoma patients, and Western blot was used to detect the expression of GLS1 protein in osteosarcoma cell lines. GLS1 siRNA was transfected into osteosarcoma U2OS cells. Western blot was used to detect the expression of GLS1 protein. MTT and clone formation assay were used to detect cell proliferation. Transwell chamber assay was used to detect migration and invasion. Western blot was used to detect the expression of CDK4 protein in GLS1 knockdown U2OS cells. CB-839 was used to treat U2OS cells. The IC50 value of CB-839 was detected by MTT. The proliferation and migration of CB-839 were detected by clone formation, scratch test, RNA seq sequencing, q-PCR and Western blot.Results: (1) GLS1 was highly expressed in osteosarcoma tissues and cell lines; (2) After transfection, compared with the control group, GLS1 protein expression and CDK4 protein expression of U2OS cells in the knockdown group were significantly down regulated. In vitro experiments showed that the proliferation, migration and invasion of U2OS cells were significantly down regulated; (3) CB-839 promoted apoptosis and inhibited the proliferation and migration of osteosarcoma cells by acting on upstream transcription factors EGR1 and FOXO1. Conclusion: GLS1 can promote the proliferation, migration and invasion of osteosarcoma cells by affecting the cell cycle of CDK4 signaling pathway, and can be used as a potential prognostic indicator and therapeutic target for osteosarcoma patients.