MAD2L1 Promotes Ewing's Sarcoma Progression Through AURKA/MYC Axis

Abstract

Abstract Background:Ewing's sarcoma (ES) is a rare and highly aggressive malignant tumor arising from bone and soft tissue. However, driver genes in ES have not been fully identified. It is extremely urgent to identify new tumor markers for ES and transform them into clinical practice Methods: Bioinformatics analysis was applied to identify the hub genes in ES. Immunohistochemistry analysis was applied to detect the protein expression levels of potential targets of MAD2L1. ES cell lines and xenograft models were used to investigateprotein functions of MAD2L1. Results:In this study, the expression level of mitotic arrest deficient 2 like 1 (MAD2L1) was found to be significantly upregulated in both ES tissues and cell lines. The expression of MAD2L1 was prominently correlated with event-free survival (EFS) and overall survival (OS). Furthermore, MAD2L1 acted as an oncogene in ES. MAD2L1 inhibition markedly reduced the proliferation and induced the apoptosis of ES cells in vitro and attenuated tumorigenesis in vivo. In terms of underlying mechanisms, we found that MAD2L1 promoted ES progression through the Aurora kinase A (AURKA)/MYC axis. Conclusion:In summary, MAD2L1 induced cell proliferation and anti-apoptosis capabilities through the AURKA/MYC axis, which provides new insights into the tumorigenesis of ES. Thus, MAD2L1 may be a potential target for clinical intervention in ES patients.