miR-145 suppresses epithelial-mesenchymal transition by targeting stem cells in Ewing sarcoma cells.

OBJECTIVES: We aimed to examine the performance of stem cell markers and epithelial-mesenchymal transition (EMT) process in miR-145 transfected EWS cells (TC71, TC106). METHODS: EWS cells were utilized for functional analysis of mir-145. Proliferation, migration, invasion and soft agar colony assay were performed to observe the alterations in migration behavior of transfected cells. Caspase assay was used to investigate the underlying reasons of proliferative inhibition in cells in whichmiR-145 is overexpressed. QRT-PCR was used to determine the role of miR-145 in EMT transcription markers and mir-145 targeted genes, KLF4, SOX2 and OCT4 expression levels. RESULTS: The miR-145 expression has been shown to be down-regulated in EWS. The miR-145 overexpression caused inhibition of proliferation and reduced migration in EWS cells through induction of apoptosis. Mir-145 suppresses EMT capacity and SOX2, KLF4 and OCT4 expression levels. CONCLUSION: This is the first time in the literature we have shown deregulation of miR-145 inhibits EMT process by targeting stem cell properties leading to the inhibition of tumor growth and metastasis in TC71 and TC106 cells. Based on these results, we propose that miR-145, as an important regulator of SOX2, KLF4 and OCT4 carries crucial roles in EWS tumorigenesis and EMT (Tab. 1, Fig. 4, Ref. 26).