[No authors listed]
Osteosarcoma (OS) is a common malignant primary bone tumor and patients with OS are known to have a poor response to chemotherapy. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules (approximately 22 nucleotides in length) and they have recently become a topic for research as regards their role in cancer therapeutics. Previous studies have reported miRâ18a expression in patients with OS is significantly decreased compared with that in normal adjacent tissue. miRâ18a belongs to the miRâ17â92 cluster encoded by the host gene MIR17HG. However, the detailed role of miRâ18a in OS remains to be determined. In this study, we demonstrated that miRâ18a mimics inhibited MG63 and Saosâ2 cell viability and migration. In addition, flow cytometry assay revealed that miRâ18a induced OS cell apoptosis. Western blot analysis indicated that the expression levels of Bclâ2 and pâAkt were downregulated, while the levels of cleaved caspaseâ3 and Bax proteins were upregulated by miRâ18a. Moreover, we demonstrated that mediator complex subunit 27 (MED27) was the target of miRâ18a through dual luciferase assay. Finally, data from in vivo experiments indicated that tumor growth in mice was significantly suppressed by miRâ18a mimics, accompanied by a decrease in the percentage of Ki67-positive cells, and by the downregulation in MED27 and pâAkt protein expression levels. The findings of the present study may aid in the clarification of the function of miRâ18a, particularly as regards its role in the regulation of OS cell apoptosis, and indicate that MED27 may be a potential novel therapeutic target in the treatment of OS.
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