MiR-92b inhibitor promoted glioma cell apoptosis via targeting DKK3 and blocking the Wnt/beta-catenin signaling pathway

J Transl Med. 2013 Dec 11:11:302. doi: 10.1186/1479-5876-11-302.

Abstract

Background: MiR-92b was upregulated in gliomas. However, the association of miR-92b with glioma cell apoptosis and survival remains unknown.

Methods: Proliferation capability of glioma cells upon tranfection with miR-92b mimics or inhibitors was detected by mutiple analyses, including MTT assays, colony formation assay. Apoptosis abilities of glioma cells were detected by flow cytometric analysis. The target of miR-92b was determined by luciferase reporter and western blot. The association of miR-92b with outcome was examined in twenty glioma patients.

Results: MiR-92b expression was significantly increased in high-grade gliomas compared with low-grade gliomas, and positively correlated with the degree of glioma infiltration. Over-expression of miR-92b increased cell proliferation, whereas knockdown of miR-92b decreased cell proliferation via modulating the levels of the target, Target prediction analysis and a dual luciferase reporting assay confirmed that the inhibitory protein-coding Dickkopf-3 gene (DKK3) was a direct target of miR-92b. Furthermore, miR-92b could regulate the expression of downstream genes of the Wnt/beta-catenin signaling pathway, such as Bcl2, c-myc and p-c-Jun, in glioma cells. Finally, the increased level of miR-92b expression in high-grade gliomas confers poorer overall survival.

Conclusions: The present data indicates that miR-92b directly regulate cell proliferation and apoptosis by targeting DKK3 and act as prognostic factors for glioma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • Apoptosis*
  • Base Sequence
  • Blotting, Western
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Chemokines
  • DNA Primers
  • Flow Cytometry
  • Glioma / pathology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • MicroRNAs / antagonists & inhibitors*
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / genetics*
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • Chemokines
  • DKK3 protein, human
  • DNA Primers
  • Intercellular Signaling Peptides and Proteins
  • MIRN92 microRNA, human
  • MicroRNAs
  • Wnt Proteins
  • beta Catenin