hsa-miR-9 controls the mobility behavior of glioblastoma cells via regulation of MAPK14 signaling elements

Oncotarget. 2016 Apr 26;7(17):23170-81. doi: 10.18632/oncotarget.6687.

Abstract

Background: Glioblastoma Multiforme (GBM) is the most common and lethal primary tumor of the brain. GBM is associated with one of the worst 5-year survival rates among all human cancers, despite much effort in different modes of treatment.

Results: Here, we demonstrate specific GBM cancer phenotypes that are governed by modifications to the MAPAKAP network. We then demonstrate a novel regulation mode by which a set of five key factors of the MAPKAP pathway are regulated by the same microRNA, hsa-miR-9.We demonstrate that hsa-miR-9 overexpression leads to MAPKAP signaling inhibition, partially by interfering with the MAPK14/MAPKAP3 complex. Further, hsa-miR-9 overexpression initiates re-arrangement of actin filaments, which leads us to hypothesize a mechanism for the observed phenotypic shift.

Conclusion: The work presented here exposes novel microRNA features and situates hsa-miR-9 as a therapeutic target, which governs metastasis and thus determines prognosis in GBM through MAPKAP signaling.

Keywords: MAPKAP signaling; cytoskeleton; glioblastoma; hsa-miR9; metastasis; pathways.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Movement*
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinase 14 / genetics
  • Mitogen-Activated Protein Kinase 14 / metabolism*
  • Prognosis
  • Signal Transduction*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • MIRN92 microRNA, human
  • MicroRNAs
  • Mitogen-Activated Protein Kinase 14