FSP1 Regulated Osteosarcoma Cells Ferroptosis, Proliferation, and Invasion by SIRT1/FBN1

Abstract

Background: Osteosarcoma (OS) belongs to the most familiar malignant bone tumor. Ferroptosis-suppress-protein 1 (FSP1), Sirtuin 1 (SIRT1), Fibrillin-1 (FBN1) are important regulators of OS progression. FSP1 is abnormally expressed in a range of tumor tissues and is a cancer promoter, but its mechanism in OS is not clear. The purpose of this research is to explore the potential function and regulatory mechanism of the possibly existed FSP1/SIRT1/FBN1 axis in OS. Methods: The relationship between FSP1, SIRT1, and FBN1 was verified by cell con-transfection assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression efficiency of FSP1, SIRT1, FBN1, and apoptotic factors. Malondialdehyde (MDA) levels in OS were detected by the thiobarbituric acid method. The viability and metastasis of OS cells were detected by cell counting kit-8 (CCK-8) and transwell assays. Results: The results indicated that FSP1 expression was upregulated in OS cells. The silencing of FSP1 suppressed viability and metastasis of OS cells, and promoted the ferroptosis. Meanwhile, the results showed that FSP1 deletion increased the expression of SIRT1, and the overexpression of SIRT1 decreased the expression of FBN1. We also found that the Sh-FBN1 reversed the inhibitory action of SIRT1 on OS cells transfected with Sh-FSP1. Conclusions: The expression pattern of FSP1 is upregulated in OS cells. The overexpression of FSP1 inhibits iron death in OS cells. In contrast, SIRT1s expression pattern is downregulated in OS, and overexpression of FSP1 suppresses SIRT1 expression. Additionally, the expression pattern of FBN1 is upregulated in OS. Overexpression of SIRT1 inhibits FBN1 expression, and this regulatory pattern can influence the metastasis and ferroptosis of OS.