MicroRNA-18a inhibits cell growth and induces apoptosis in osteosarcoma by targeting MED27

Abstract

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 miR-18a expression in patients with OS is significantly decreased compared with that in normal adjacent tissue. miR-18a belongs to the miR-17-92 cluster encoded by the host gene MIR17HG. However, the detailed role of miR-18a in OS remains to be determined. In this study, we demonstrated that miR-18a mimics inhibited MG63 and Saos-2 cell viability and migration. In addition, flow cytometry assay revealed that miR-18a induced OS cell apoptosis. Western blot analysis indicated that the expression levels of Bcl-2 and p-Akt were downregulated, while the levels of cleaved caspase-3 and Bax proteins were upregulated by miR-18a. Moreover, we demonstrated that mediator complex subunit 27 (MED27) was the target of miR-18a through dual luciferase assay. Finally, data from in vivo experiments indicated that tumor growth in mice was significantly suppressed by miR-18a mimics, accompanied by a decrease in the percentage of Ki67-positive cells, and by the downregulation in MED27 and p-Akt protein expression levels. The findings of the present study may aid in the clarification of the function of miR-18a, 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.