miR‑181d promotes cell proliferation via the IGF1/PI3K/AKT axis in glioma

Mol Med Rep. 2020 Nov;22(5):3804-3812. doi: 10.3892/mmr.2020.11464. Epub 2020 Aug 26.

Abstract

Glioma is a malignant brain cancer that exhibits high invasive ability and poor prognosis. MicroRNA (miR)‑181d has been reported to be involved in the development of glioma. Therefore, the aim of the present study was to investigate whether miR‑181d affected cellular progression by influencing the insulin like growth factor (IGF1)/PI3K/AKT axis. Western blot analysis was performed to analyze the expression levels of specific proteins, and a Cell Counting Kit‑8 assay was used to assess the proliferative ability of cells. Cell cycle progression and cellular apoptosis were both measured using flow cytometry. The results indicated that miR‑181d promoted cellular proliferation and cell cycle progression, while suppressing cellular apoptosis via the IGF1/PI3K/AKT axis. It was demonstrated that the IGF1 and PI3K/AKT inhibitors reversed these observed functions of miR‑181d. Furthermore, miR‑181d enhanced the growth of glioma xenografts in vivo, promoted cell cycle progression and suppressed cellular apoptosis within glioma xenograft tissues. Therefore, this newly identified miR‑181d/IGF1/PI3K/AKT axis may provide novel insights into the pathogenesis of glioma.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Chromones / pharmacology
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Imidazoles / pharmacology
  • Insulin-Like Growth Factor I / antagonists & inhibitors
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Pyrazines / pharmacology
  • Signal Transduction / genetics*
  • Transfection
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • 3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol
  • Chromones
  • IGF1 protein, human
  • Imidazoles
  • MicroRNAs
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Pyrazines
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Insulin-Like Growth Factor I
  • Proto-Oncogene Proteins c-akt