MicroRNA-21 promotes glioma cell proliferation and inhibits senescence and apoptosis by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway

CNS Neurosci Ther. 2018 May;24(5):369-380. doi: 10.1111/cns.12785. Epub 2018 Jan 5.

Abstract

Aims: Our study aims to investigate the effect of microRNA-21 (miR-21) on the proliferation, senescence, and apoptosis of glioma cells by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway.

Methods: Glioma tissues and brain tissues were collected for this study after surgical decompression for traumatic brain injury. RT-qPCR was employed to measure mRNA levels of miR-21, SPRY1, PTEN, PI3K, and AKT, and Western blotting was conducted to determine protein levels of SPRY1, PTEN, PI3K, AKT, p-AKT, Caspase-3, Caspase-9, P53, GSK3, and p-GSK3. Human glioma U87 cells were assigned into the blank, negative control (NC), miR-21 mimics, miR-21 inhibitors, siRNA-SPRY1, and miR-21 inhibitors + siRNA-SPRY1 groups, with human HEB cells serving as the normal group. Cell proliferation, cell cycle, and apoptosis were determined by MTT and flow cytometry, respectively.

Results: Compared with control group, an increased expression of miR-21, PI3K, AKT, p-AKT, P53, and p-GSK3, and a decreased expression of SPRY1, PTEN, Caspase-3, and Caspase-9 were observed in the glioma group, and no significant differences were found in the expression of GSK3. SPRY1 was verified to be the target gene of miR-21. Compared with the blank and NC groups, levels of PI3K, AKT, p-AKT, P53, and p-GSK3 increased while levels of SPRY1, PTEN, Caspase-3, and Caspase-9 decreased in the miR-21 mimics and siRNA-SPRY1 groups; the miR-21 inhibitors group reversed the tendency; furthermore, the miR-21 inhibitors group showed decreased cell proliferation but promoted apoptosis, which were opposite to the results of the miR-21 mimics and siRNA-SPRY1 groups.

Conclusion: MicroRNA-21 might promote cell proliferation and inhibit cell senescence and apoptosis of human glioma cells by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway.

Keywords: PTEN/PI3K/AKT signaling pathway; Sprouty1; apoptosis; cell senescence; glioma; microRNA-21.

Publication types

  • Retracted Publication

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis / physiology*
  • Brain / metabolism
  • Brain Neoplasms / metabolism*
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology*
  • Cellular Senescence / physiology*
  • Female
  • Glioma / metabolism*
  • Humans
  • Male
  • Membrane Proteins / metabolism
  • MicroRNAs / metabolism*
  • Middle Aged
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Young Adult

Substances

  • MIRN21 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Phosphoproteins
  • SPRY1 protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human