Osteosarcoma (OS) is the most common type of primary bone tumor that 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 long noncoding RNAs (lncRNA) XIST (X-inactive specific transcript) has been reported to have oncogenic roles in various malignant tumors including OS. However, its molecular mechanisms in OS migration and invasion are still under investigation. In the current study, we demonstrate that XIST is significantly upregulated in 30 pairs of OS tissues compared with their matched adjacent nontumor tissues by the quantitative reverse transcription polymerase chain reaction. 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 that 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 messenger RNA 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.
Keywords: XIST; epithelial-to-mesenchymal transition; lncRNA; miR-153; osteosarcoma.
© 2020 International Federation for Cell Biology.