MiRNA-188-5p alleviates the progression of osteosarcoma via target degrading CCNT2

Eur Rev Med Pharmacol Sci. 2020 Jan;24(1):29-35. doi: 10.26355/eurrev_202001_19892.

Abstract

Objective: The aim of this study was to investigate the biological role of microRNA-188-5p (miRNA-188-5p) in mediating the progression of osteosarcoma by degrading CCNT2.

Patients and methods: The relative expression levels of miRNA-188-5p and CCNT2 in osteosarcoma tissues and para-cancerous normal tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, their expression levels in osteosarcoma cell lines were examined. The regulatory effects of miRNA-188-5p on the proliferative ability and cell cycle progression of osteosarcoma cells were evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. Dual-Luciferase reporter gene assay was applied to verify the binding relationship between miRNA-188-5p and CCNT2. Furthermore, rescue experiments were conducted to clarify the role of miRNA-188-5p/CCNT2 in mediating the progression of osteosarcoma.

Results: MiRNA-188-5p was lowly expressed in osteosarcoma tissues when compared with paracancerous normal tissues. Overexpression of miRNA-188-5p significantly suppressed the proliferative ability and arrested cell cycle progression of osteosarcoma cells. However, knockdown of miRNA-188-5p obtained the opposite trends. The Dual-Luciferase reporter gene assay verified the binding relationship between miRNA-188-5p and CCNT2. The expression level of CCNT2 in HOS and MG-63 cells was markedly downregulated after transfection of miRNA-188-5p mimics. In addition, overexpression of CCNT2 could partially reverse the inhibitory effect of miRNA-188-5p on the proliferative ability and cell cycle progression of osteosarcoma cells.

Conclusions: MiRNA-188-5p is downregulated in osteosarcoma. Furthermore, it suppresses the proliferative ability and cell cycle progression of osteosarcoma cells via target degrading CCNT2.

MeSH terms

  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Proliferation
  • Cells, Cultured
  • Cyclin T / genetics
  • Cyclin T / metabolism*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology

Substances

  • CCNT2 protein, human
  • Cyclin T
  • MIRN188 microRNA, human
  • MicroRNAs