The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo Journal Article

   

Authors:	Huse, J. T.; Brennan, C.; Hambardzumyan, D.; Wee, B.; Pena, J.; Rouhanifard, S. H.; Sohn-Lee, C.; Le Sage, C.; Agami, R.; Tuschl, T.; Holland, E. C.
Article Title:	The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo
Abstract:	Activated oncogenic signaling is central to the development of nearly all forms of cancer, including the most common class of primary brain tumor, glioma. Research over the last two decades has revealed the particular importance of the Akt pathway, and its molecular antagonist PTEN (phosphatase and tensin homolog), in the process of gliomagenesis. Recent studies have also demonstrated that microRNAs (miRNAs) may be responsible for the modulation of cancer-implicated genes in tumors. Here we report the identification miR-26a as a direct regulator of PTEN expression. We also show that miR-26a is frequently amplified at the DNA level in human glioma, most often in association with monoallelic PTEN loss. Finally, we demonstrate that miR-26a-mediated PTEN repression in a murine glioma model both enhances de novo tumor formation and precludes loss of heterozygosity and the PTEN locus. Our results document a new epigenetic mechanism for PTEN regulation in glioma and further highlight dysregulation of Akt signaling as crucial to the development of these tumors. © 2009 by Cold Spring Harbor Laboratory Press.
Keywords:	immunohistochemistry; platelet derived growth factor; unclassified drug; genetics; nonhuman; pathophysiology; brain tumor; glioma; animal cell; mouse; animal; metabolism; animals; mice; cells, cultured; gene overexpression; reverse transcription polymerase chain reaction; microrna; animal experiment; animal model; histology; genetic transduction; kaplan-meiers estimate; disease model; rna; gene expression regulation; in situ hybridization; gene expression regulation, neoplastic; cell culture; western blotting; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; pten phosphohydrolase; retrovirus vector; murinae; tumor model; heterozygosity loss; helicase; pten protein, mouse; kaplan meier method; micrornas; akt; pten; disease models, animal; loss of heterozygosity; pten protein, human; cell strain 3t3; nih 3t3 cells; mir-26a; genomic dna; microrna 26a; mirn26a microrna, human; dna helicases
Journal Title:	Genes and Development
Volume:	23
Issue:	11
ISSN:	0890-9369
Publisher:	Cold Spring Harbor Laboratory Press
Date Published:	2009-06-01
Start Page:	1327
End Page:	1337
Language:	English
DOI:	10.1101/gad.1777409
PUBMED:	19487573
PROVIDER:	scopus
PMCID:	PMC2701585
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-66149173789&partnerID=40&md5=5e0bee4bdc6fd5eed1dd1147a8eda1d3
Notes:	--- - "Cited By (since 1996): 27" - "Export Date: 30 November 2010" - "CODEN: GEDEE" - "Source: Scopus"

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