Osteosarcoma (OS) is one of the most common primary bone malignancies, with the survival rate of patients with OS remaining low. Therefore, we conducted this study to identify the potential role combination of both MSH6 gene silencing and cisplatin (DDP) plays in OS cell proliferation and apoptosis. Microarray‐based gene expression profiling was used to identify the differentially expressed genes (DEGs) in patients with OS, as well as microRNAs (miRNAs) that regulate the candidate gene. OS tissues from 67 patients with OS along with normal tissues from 24 amputee patients were collected for detection of the positive expression of mutS homolog 6 (MSH6) protein, mRNA, and protein expressions of c‐myc, cyclin D1, l‐2, B‐cell lymphoma 2 (Bcl‐2), Stathmin, proliferating cell nuclear antigen (PCNA), and Bcl‐2‐associated X (Bax). Moreover, after MSH6 silencing and DDP were treated on the selected human OS cell line MG63 with the highest expression of MSH6, cell viability, cell cycle distribution, and apoptosis were detected. The microarray analysis showed that MSH6 was upregulated in OS chip data. Furthermore, silencing MSH6 combined with DDP reduced expressions of c‐myc, cyclin D1, Bcl‐2, Stathmin, and PCNA, and elevated Bax expression, whereas inhibiting OS cell viability, impeding cell cycle distribution, and inducing apoptosis. In conclusion, our preliminary results indicated that the combination of MSH6 gene silencing coupled with DDP may have a better effect on the inhibition of OS cell proliferation and promote apoptosis, potentially providing targets for the OS treatment.

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,, 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 exp ression 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 ind icated 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 overexpres sion 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.