MicroRNA-18a Inhibits Cell Growth and Induces Apoptosis in Osteosarcoma by Targeting MED27

Int J Oncol. 2018 Jul;53(1):329-338. doi: 10.3892/ijo.2018.4374. Epub 2018 Apr 16.

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.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Cell Survival / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mediator Complex / genetics*
  • Mice
  • MicroRNAs / genetics*
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Xenograft Model Antitumor Assays

Substances

  • BCL2 protein, human
  • MED27 protein, human
  • MIRN18A microRNA, human
  • Mediator Complex
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-akt