Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme

Oncotarget. 2016 Jan 26;7(4):4746-59. doi: 10.18632/oncotarget.6621.

Abstract

MiR-671-5p is encoded by a gene localized at 7q36.1, a region amplified in human glioblastoma multiforme (GBM), the most malignant brain cancer. To investigate whether expression of miR-671-5p were altered in GBM, we analyzed biopsies from a cohort of forty-five GBM patients and from five GBM cell lines. Our data show significant overexpression of miR-671-5p in both biopsies and cell lines. By exploiting specific miRNA mimics and inhibitors, we demonstrated that miR-671-5p overexpression significantly increases migration and to a less extent proliferation rates of GBM cells. Through a combined in silico and in vitro approach, we identified CDR1-AS, CDR1, VSNL1 as downstream miR-671-5p targets in GBM. Expression of these genes significantly decreased both in GBM biopsies and cell lines and negatively correlated with that of miR-671-5p. Based on our data, we propose that the axis miR-671-5p / CDR1-AS / CDR1 / VSNL1 is functionally altered in GBM cells and is involved in the modification of their biopathological profile.

Keywords: cell networks; circular RNAs (circRNAs); glioblastoma multiforme (GBM); microRNAs (miRNAs); non coding RNAs (ncRNAs).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Biomarkers, Tumor
  • Brain / metabolism*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Case-Control Studies
  • Cell Proliferation
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Staging
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurocalcin / genetics
  • Neurocalcin / metabolism*
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Wound Healing

Substances

  • Autoantigens
  • Biomarkers, Tumor
  • CDR1 protein, human
  • MIRN671 microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • Neurocalcin
  • RNA, Messenger
  • VSNL1 protein, human