LncRNA TUG1 promotes Ewing's sarcoma cell proliferation, migration, and invasion via the miR-199a-3p-MSI2 signaling pathway.

The aim of this study was to investigate the roles and potential mechanisms of long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in the proliferation, migration, and invasion of Ewing's sarcoma cells. RT-qPCR was used to detect the expression of TUG1, microRNA-199a-3p (miR-199a-3p), and musashi2 (MSI2) in Ewing's sarcoma tissues and cell lines. Kaplan-Meier overall survival curves showed the survival rates of Ewing's sarcoma patients with high and low expression of TUG1. The association between the expressions of TUG1/MSI2 and miR-199a-3p in Ewing's sarcoma tissues was assessed by Pearson's correlation analysis. Cell proliferation, migration, and invasion were detected by CCK8 assay and Transwell assay, respectively. The protein level of MSI2 was determined using western blotting. The interaction between TUG1/MSI2 and miR-199a-3p was validated by the dual-luciferase reporter assay. The levels of TUG1 and MSI2 were increased, while the level of miR-199a-3p was decreased in Ewing's sarcoma tissues and cells. High expression of TUG1 or MSI2 indicated a decreased overall survival rate of Ewing's sarcoma patients. TUG1/MSI2 level was negatively correlated with miR-199a-3p level. While TUG1 level was positively correlated with MSI2 level. In Ewing sarcoma cells, knockdown of TUG1/MSI2 or overexpression of miR-199a-3p inhibited cell proliferation, migration, and invasion, whereas the overexpression of TUG1/MSI2 presented the opposite results. TUG1 functioned as a competing endogenous RNA to regulate MSI2 expression by sponging miR-199a-3p. Finally, miR-199a-3p inhibitor or MSI2 overexpression counteracted the TUG1 knockdown-mediated inhibitory effect on Ewing's sarcoma cell proliferation, migration, and invasion. TUG1 promotes proliferation, migration, and invasion of Ewing's sarcoma cells via sequestering miR-199a-3p to enhance the MSI2 expression, suggesting that TUG1 might be a potential target for treating Ewing's sarcoma.