Long non-coding RNA Ftx promotes osteosarcoma progression via the epithelial to mesenchymal transition mechanism and is associated with poor prognosis in patients with osteosarcoma

摘要

Objective: Long non-coding RNA Ftx (lncRNA Ftx) is involved in a variety of cancers. However, the association between lncRNA Ftx and osteosarcoma is still unclear. In this study, we investigated the correlation between lncRNA Ftx and osteosarcoma, and the regulative effect of Ftx on the migration and invasion of osteosarcoma cells, as well as its molecular mechanism. Methods: Expression levels of lncRNA Ftx in osteosarcoma tissues and adjacent non-tumor corresponding tissues (ANCTs) were detected using quantitative real-time PCR (qRT-PCR). Differences in patient survival were determined by the Kaplan-Meier method and a log-rank test. The Cox regression analysis was used for univariate and multivariate analyses of prognostic values. Human osteosarcoma cell lines Saos2 and HOS were transfected with the pcDNA-Ftx constructs. The scratch wound healing assay and Transwell assay were used to assess cell migration and invasion capability, respectively. Western blot analysis was conducted to investigate the expression of mesenchymal and epithelial markers. Results: The results showed that the lncRNA Ftx group was higher in osteosarcoma tissues compared with the ANCTs group. Expression of lncRNA Ftx was correlated with the clinical stage and distant metastasis (P<0.05). The overall survival rate was lower in the high lncRNA Ftx group than in the low lncRNA Ftx group (log-rank test, P<0.05). Multivariate analysis revealed that in osteosarcoma patients, higher lncRNA MEG3, advanced clinical stage, and distant metastasis were all independent predictors of overall survival. Cell research showed that transfection of lncRNA Ftx significantly promoted the migration and invasion ability of osteosarcoma cells. In addition, E-cadherin was decreased, while N-cadherin and Snail-1 were increased, at both the protein and mRNA levels. Pre-treatment with Snail-1 siRNA abrogated the promotion effect of Ftx on the migration and invasion of osteosarcoma cells. Conclusions: Increased expression of lncRNA Ftx could not only be a biomarker for progression and prognosis of osteosarcoma, but also could regulate the development of osteosarcoma via the epithelial to mesenchymal transition (EMT) mechanism.