The neuronal microRNA miR-326 acts in a feedback loop with Notch and has therapeutic potential against brain tumors Academic Article uri icon

Overview

MeSH Major

  • Gene Expression Regulation, Neoplastic
  • Glioma
  • MicroRNAs
  • Receptor, Notch1
  • Signal Transduction

abstract

  • Little is known of microRNA interactions with cellular pathways. Few reports have associated microRNAs with the Notch pathway, which plays key roles in nervous system development and in brain tumors. We previously implicated the Notch pathway in gliomas, the most common and aggressive brain tumors. While investigating Notch mediators, we noted microRNA-326 was upregulated following Notch-1 knockdown. This neuronally expressed microRNA was not only suppressed by Notch but also inhibited Notch proteins and activity, indicating a feedback loop. MicroRNA-326 was downregulated in gliomas via decreased expression of its host gene. Transfection of microRNA-326 into both established and stem cell-like glioma lines was cytotoxic, and rescue was obtained with Notch restoration. Furthermore, miR-326 transfection reduced glioma cell tumorigenicity in vivo. Additionally, we found microRNA-326 partially mediated the toxic effects of Notch knockdown. This work demonstrates a microRNA-326/Notch axis, shedding light on the biology of Notch and suggesting microRNA-326 delivery as a therapy.

publication date

  • December 2, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2823067

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.4966-09.2009

PubMed ID

  • 19955368

Additional Document Info

start page

  • 15161

end page

  • 8

volume

  • 29

number

  • 48