The Neuronal MicroRNA miR-326 Acts in a Feedback Loop with Notch and Has Therapeutic Potential against Brain Tumors

被引：189

作者：

Kefas, Benjamin

Comeau, Laurey

Floyd, Desiree H.

Seleverstov, Oleksandr

Godlewski, Jakub ^{[2
]}

Schmittgen, Tom ^{[3
]}

Jiang, Jinmai ^{[3
]}

diPierro, Charles G. ^{[4
]}

Li, Yunqing ^{[5
,6
]}

Chiocca, E. Antonio ^{[2
]}

Lee, Jeongwu ^{[7
]}

Fine, Howard ^{[7
]}

Abounader, Roger

Lawler, Sean ^{[2
]}

Purow, Benjamin ^{[1
]}

机构：

[1] Univ Virginia Hlth Syst, Old Med Sch, Dept Neurol, Div Neurooncol, Charlottesville, VA 22908 USA

[2] Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci, Columbus, OH 43210 USA

[3] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA

[4] Univ VIrginia Hlth Syst, Dept Pathol, Charlottesville, VA 22908 USA

[5] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[6] Hugo W Moser Res Inst Kennedy Krieger, Baltimore, MD 21205 USA

[7] Natl Inst Neurol Disorders & Stroke, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF NEUROSCIENCE | 2009年 / 29卷 / 48期

基金：

美国国家卫生研究院;

关键词：

CELL-LINES; PROTEIN-KINASE; STEM-CELLS; ACTIVATION; EXPRESSION; APOPTOSIS; NEUROGENESIS; GLIOBLASTOMA; INHIBITION; RECEPTOR;

D O I：

10.1523/JNEUROSCI.4966-09.2009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

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.

引用

页码：15161 / 15168

页数：8

共 33 条

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