LncRNA-XIST promotes the oxidative stress-induced migration, invasion and epithelial to mesenchymal transition of osteosarcoma cancer cells through miR-153-SNAI1 axis.

Osteosarcoma (OS) is the most common type of primary bone tumor which exhibits invasive growth and long-distance organ metastasis. Thus, investigating the specifically targeted therapeutic agents against metastatic osteosarcoma depends on understanding the molecular mechanisms. The lncRNA XIST (X inactive-specific transcript) has been reported to have oncogenic roles in various malignant tumors including OS. However, its molecular mechanisms in osteosarcoma (OS) migration and invasion are still under investigation. In the current study, we demonstrate XIST is significantly upregulated in 30 pairs of OS tissues compared with their matched adjacent non-tumor tissues by qRT-PCR. Overexpression of XIST significantly induced the invasion, migration and the epithelial to mesenchymal transition (EMT) phenotype. The epithelial marker, E-cadherin was effectively suppressed by XIST overexpression. On the other way, the mesenchymal marker, Fibronectin, Snail and Vimentin were significantly activated by exogenous XIST overexpression. Furthermore, we observed XIST was upregulated by the oxidative stress-induced EMT. Bioinformatical analysis indicated miR-153 has multiple biding sites for XIST and miR-153 was inversely suppressed by oxidative stress. XIST was verified to directly downregulate miR-153 via sponging. We identified the mesenchymal marker, SNAI1 was a direct mRNA target of miR-153. Importantly, inhibiting XIST successfully blocked the H2 O2 -induced EMT of OS cells. In conclusion, this work demonstrates that lncRNA-XIST promotes the oxidative stress-induced OS cell invasion, migration and EMT through the miR-153/SNAI1 pathway, presenting lncRNA-XIST as a promising therapeutic target for treating metastatic OS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.