miR-92a-3p Exerts Various Effects in Glioma and Glioma Stem-Like Cells Specifically Targeting CDH1/β-Catenin and Notch-1/Akt Signaling Pathways

Int J Mol Sci. 2016 Oct 27;17(11):1799. doi: 10.3390/ijms17111799.

Abstract

MicroRNAs (miRNAs) are implicated in the regulation of tumor progression and stemness of cancer stem-like cells. Recently, miR-92a-3p was reported to be up-regulated in human glioma samples. Nevertheless, the precise role of miR-92a-3p in glioma cells and glioma stem-like cells (GSCs) has not been fully elucidated. It is necessary to clarify the function of miR-92a-3p in glioma and GSCs to develop novel therapeutic approaches for glioma patients. In the present study, we applied methyl-thiazolyl-tetrazolium (MTT) assay and Transwell assay to measure the proliferation rate and metastatic potential of glioma cells. Meanwhile, the self-renewal ability of GSCs was detected by tumor sphere formation assay. The results revealed that down-regulation of miR-92a-3p suppressed the glioma cell malignancy in vitro. Moreover, knockdown of miR-92a-3p led to a reduction of tumorgenesis in vivo. Interestingly, we also observed that up-regulation of miR-92a-3p could inhibit the stemness of GSCs. Subsequent mechanistic investigation indicated that cadherin 1 (CDH1)/β-catenin signaling and Notch-1/Akt signaling were the downstream pathways of miR-92a-3p in glioma cells and GSCs, respectively. These results suggest that miR-92a-3p plays different roles in glioma cells and GSCs through regulating different signaling pathways.

Keywords: CDH1; Notch-1; glioma; glioma stem-like cells; miR-92a-3p.

MeSH terms

  • Animals
  • Antigens, CD
  • Cadherins / biosynthesis
  • Cadherins / genetics*
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Mice
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Neoplastic Stem Cells / pathology
  • Oncogene Protein v-akt / genetics
  • Receptor, Notch1 / genetics*
  • Signal Transduction / genetics
  • Xenograft Model Antitumor Assays
  • beta Catenin / genetics

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • MIRN92 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • Receptor, Notch1
  • beta Catenin
  • Oncogene Protein v-akt