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miR-17-5p promotes the growth of osteosarcoma in a BRCC2-dependent mechanism
Wei Wang1, Liang Zhang2, Ke Zheng1
1Department of Bone Soft Surgery, Liaoning Provincial Tumor Hospital, Shenyang, Liaoning 110042, P.R. China.
Abstract:
MicroRNA-17-5p has been proven upregulated in many human malignancies and correlated with tumor progression. However, its expression and clinical significance in osteosarcoma is still unclear. Thus, the aim of the present study was to explore the effects of miR-17-5p in osteosarcoma tumorigenesis and development. The expression level of miR-17-5p was quantified by quantitative real-time reverse-transcriptase-polymerase chain reaction in primary osteosarcoma tissues and osteosarcoma cell lines. MTT, Transwell and matrigel assays were used to test the proliferation, migration and invasion of miR-17-5p transfection osteosarcoma cells, and a mouse model was used to investigate tumorigenesis. The expression levels of miR-17-5p in osteosarcoma tissues were significantly higher than those in corresponding non-cancerous bone tissues. In addition, miR-17-5p upregulation more frequently occurred in osteosarcoma specimens with advanced clinical stage, positive distant metastasis and poor response to neo-adjuvant chemotherapy. After miR-17-5p transfection, cell proliferation, migration, invasion and tumorigenesis in the osteosarcoma cells were significantly promoted. We further demonstrated that BRCC2 is a direct target of miR-17-5p. These findings indicate that miR-17-5p may act not only as a novel diagnostic and prognostic marker, but also as a potential target for molecular therapy of osteosarcoma.
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