| Literature DB >> 19955368 |
Benjamin Kefas1, Laurey Comeau, Desiree H Floyd, Oleksandr Seleverstov, Jakub Godlewski, Tom Schmittgen, Jinmai Jiang, Charles G diPierro, Yunqing Li, E Antonio Chiocca, Jeongwu Lee, Howard Fine, Roger Abounader, Sean Lawler, Benjamin Purow.
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.Entities:
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Year: 2009 PMID： 19955368 PMCID： PMC2823067 DOI： 10.1523/JNEUROSCI.4966-09.2009
Source DB: PubMed Journal: J Neurosci ISSN： 0270-6474 Impact factor: 6.167