miR-137 is frequently down-regulated in glioblastoma and is a negative regulator of Cox-2

Eur J Cancer. 2012 Nov;48(16):3104-11. doi: 10.1016/j.ejca.2012.02.007. Epub 2012 Mar 7.

Abstract

MicroRNAs are strongly implicated in cancer but their specific roles and functions in the major cancers have yet to be fully elucidated. In this study, we defined the expression and function of miR-137, which we found to be downregulated in glioma samples and glioma cells by qRT-PCR. Ectopic expression of miR-137 in glioma cell lines inhibited proliferation and invasion. Using computational and expression analysis, Cox-2 was identified as a candidate target of miR-137. Reporter assay with 3'UTR of Cox-2 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-137, providing strong evidence that miR-137 was a direct regulator of Cox-2. Expression analysis further revealed that Cox-2 was elevated in glioma and associated with survival of patients. Furthermore, we observed that Cox-2 knockdown resulted in effects similar to those with miR-137 transfection in glioma cells. In conclusion, our study demonstrates that miR-137 deregulation is common in glioma, and restoration of its function inhibits cell proliferation and invasion, suggesting that miR-137 may act as a tumour suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chi-Square Distribution
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Down-Regulation
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Genetic Therapy
  • Glioblastoma / enzymology
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Glioblastoma / therapy
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • MIRN137 microRNA, human
  • MicroRNAs
  • Cyclooxygenase 2
  • PTGS2 protein, human