MiR-24 regulates the proliferation and invasion of glioma by ST7L via β-catenin/Tcf-4 signaling

Cancer Lett. 2013 Feb 28;329(2):174-80. doi: 10.1016/j.canlet.2012.10.025. Epub 2012 Nov 7.

Abstract

MicroRNAs are strongly implicated as affecting glioma, but their specific roles and functions have yet to be fully elucidated. In this study, we defined the expression and function of miR-24, which we found to be upregulated in glioma samples and glioma cells by qRT-PCR. Downregulation of miR-24 in glioma cell lines inhibited proliferation and invasion and induced apoptosis. Using computational and expression analysis, ST7L was identified as a candidate target of miR-24. A reporter assay with the 3'UTR of ST7L cloned downstream of a luciferase gene showed increased luciferase activity in the absence of miR-24, providing strong evidence that miR-24 is a direct regulator of ST7L. Furthermore, we observed that restoration of ST7L activity resulted in effects that were similar to those from transfecting a miR-24 inhibitor into glioma cells. Mechanistic investigation revealed that the deletion of miR-24 suppressed β-catenin/Tcf-4 transcription activity by targeting ST7L. In conclusion, our study demonstrates that miR-24 upregulation is common in glioma and that suppression of miR-24 expression inhibits cell proliferation and invasion, suggesting that miR-24 may act as an oncogene in glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis
  • Base Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Binding Sites
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation*
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • MicroRNAs / physiology
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Signal Transduction
  • Transcription Factor 4
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins
  • beta Catenin / metabolism*

Substances

  • 3' Untranslated Regions
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MIRN24 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
  • ST7L protein, human
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors
  • Tumor Suppressor Proteins
  • beta Catenin