MicroRNA-34b promotes proliferation, migration and invasion of Ewing's sarcoma cells by downregulating Notch1

Ewing's sarcoma is the second most frequent bone and soft tissue sarcoma, which is commonly driven by the Ewing's sarcoma breakpoint region 1-friend leukemia integration 1 transcription factor (EWS-FLI1) fusion gene. Since microRNAs (miRs) can act as either oncogenes or tumor suppressor genes in human cancer, and miR-34b has been reported to act as a tumor suppressor, the role of miR-34b in Ewing's sarcoma was investigated in the present study. The results demonstrated that miR-34b expression levels were higher in tumor samples compared within normal tissue samples. Notably, miR-34b expression levels were significantly higher in EWS-FLI1-positive samples compared within EWS-FLI1-negative samples. The effects of miR-34b expression on cell proliferation, migration and invasion were also examined. miR-34b expression was inhibited using small interfering (si)RNA targeting the fusion gene. Transfection of a miR-34b precursor sequence into siRNA-treated tumor cells resulted in a significant increase in cell growth, migration and invasion compared within the control group. In addition, the adhesive ability was increased in the Ewing's sarcoma cell line RD-ES, but not A673, following miR-34b upregulation. Conversely, downregulation of miR-34b expression led to a significant decrease in cell growth, migration and invasion. Notch has previously been reported to serve either oncogenic or tumor suppressive roles in human cancer. The results indicated that Notch1 and its target genes, Hes family BHLH transcription factor 1 and Hes-related family BHLH transcription factor with YRPW motif 1, were suppressed by miR-34b directly In conclusion, EWS-FLI1 may modulate miR-34b expression directly or indirectly, and miR-34b potentially has an oncogenic role in Ewing's sarcoma by downregulating Notch1.