MiR-135a functions as a selective killer of malignant glioma

Oncogene. 2012 Aug 23;31(34):3866-74. doi: 10.1038/onc.2011.551. Epub 2011 Dec 5.

Abstract

Glioma is the most common and fatal primary brain tumor. Thus far, therapeutic strategies to efficiently and specifically antagonize glioma are limited and poorly developed. Here we report that glia-enriched miR-135a, a microRNA that is dramatically downregulated in malignant glioma and correlated with the pathological grading, is capable of inducing mitochondria-dependent apoptosis of malignant glioma by regulating various genes including STAT6, SMAD5 and BMPR2, as well as affecting the signaling pathway downstream. Moreover, this lethal effect is selectively towards malignant glioma cells, but not neurons and glial cells, through a novel mechanism. Our findings suggest an important role of miR-135a in glioma etiology and provide a potential candidate for malignant glioma therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Base Sequence
  • Blotting, Western
  • Bone Morphogenetic Protein Receptors, Type II / genetics
  • Bone Morphogenetic Protein Receptors, Type II / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cells, Cultured
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / pathology
  • Glioma / therapy
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • RNA Interference
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / metabolism
  • Sequence Homology, Nucleic Acid
  • Smad5 Protein / genetics
  • Smad5 Protein / metabolism
  • Tumor Burden / genetics
  • Xenograft Model Antitumor Assays*

Substances

  • MIRN135 microRNA, human
  • MicroRNAs
  • STAT6 Transcription Factor
  • Smad5 Protein
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II