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

Genes and Development - Tập 23 Số 11 - Trang 1327-1337 - 2009
Jason T. Huse1,2,3, Cameron Brennan1,4, Dolores Hambardzumyan1,2, Boyoung Wee2, John Pena5, Sara H. Rouhanifard5, Cherin Sohn-Lee5, Carlos le Sage6, Reuven Agami6, Thomas Tuschl5, Eric C. Holland1,2,4
1Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA;
2Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
4Department of Surgery (Neurosurgery), Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA;
5Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, New York, New York 10065, USA;
6Division of Gene Regulation, The Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands

Tóm tắt

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.

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Genes and Development

Tập 23 Số 11

1327-1337

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