The emerging role of the MiR-1272-ADAM9-CDCP1 signaling pathway in the progression of glioma

Aging (Albany NY). 2020 Nov 26;13(1):894-909. doi: 10.18632/aging.202196. Epub 2020 Nov 26.

Abstract

Glioma is a primary, malignant, and aggressive brain tumor in adults. To develop new therapeutic strategies for glioma, we must determine its underlying mechanisms. In the present study, we aimed to investigate the potential role of miR-1272-ADAM9-CDCP1 signaling in the progression of glioma. We found that ectopic expression of miR-1272 produced significant inhibitory effects on cell proliferation and migration and was associated with cell cycle G0/G1 arrest in A172 and SHG44 glioma cells. Using the luciferase reporter assay, we identified ADAM9 as a target of miR-1272. The expression of ADAM9 was markedly decreased or increased after overexpression or inhibition, respectively, of miR-1272 in glioma cells. Moreover, overexpression of ADAM9 reversed the inhibitory effects of miR-1272 on glioma cell progression. Furthermore, CDCP1 served as a potential downstream molecule of miR-1272/ADAM9 signaling in glioma and promoted the proliferation and migration of glioma. Results derived from clinical samples and online databases confirmed correlations between the expression of ADAM9 and CDCP1 and both the severity and prognosis of glioma. In conclusion, these results suggest that miR-1272 and CDCP1 may act as novel regulators in glioma. The miR-1272/ADAM9/CDCP1 pathway may serve as a potential candidate pathway for the prevention of glioma.

Keywords: ADAM9; CDCP1; glioma; miR-1272.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics*
  • ADAM Proteins / metabolism
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Astrocytoma / genetics
  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Signal Transduction

Substances

  • Antigens, Neoplasm
  • CDCP1 protein, human
  • Cell Adhesion Molecules
  • MIRN1272 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • ADAM Proteins
  • ADAM9 protein, human