TNF-α/miR-155 axis induces the transformation of osteosarcoma cancer stem cells independent of TP53INP1.

MicroRNA-155 (miR-155) has been identified to be overexpressed in various human cancers including osteosarcoma. However, whether the up-regulation of miR-155 is associated with osteosarcoma cancer stem cells (CSCs) is not well understood. In the present study, we showed that miR-155 induced the acquisition of stem-like features in U2OS osteosarcoma cells by increasing the expression of both CSCs surface markers (CD24, CD90, CD133) and CSC-related transcriptional factors (Nanog, SOX2, Oct4, Bim-1). Inflammatory factor TNF-α upregulated the miR-155 expression in U2OS cells and formed a feedback regulatory loop with miR-155. Furthermore, TNF-α/miR-155 axis promoted the cell proliferation, invasion and epithelial-mesenchymal transition (EMT) process in a TP53INP1 independent manner. We also revealed that TNF-α/miR-155 axis induced osteosarcoma CSCs transformation via ERK signaling pathway. These results indicate a crucial role of miR-155 in the acquisition of osteosarcoma CSC phenotype and miR-155 may serve as a potential target in future osteosarcoma therapy.