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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Regulation of insulin-like growth factor-mammalian target of rapamycin signaling by MicroRNA in childhood adrenocortical tumors
Cancer Research, Volume 70, No. 11, Year 2010
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Description
MicroRNAs (miRNAs) act at the posttranscriptional level to control gene expression in virtually every biological process, including oncogenesis. Here, we report the identification of a set of miRNAs that are differentially regulated in childhood adrenocortical tumors (ACT), including miR-99a and miR-100. Functional analysis of these miRNAs in ACT cell lines showed that they coordinately regulate expression of the insulin-like growth factor-mammalian target of rapamycin (mTOR)-raptor signaling pathway through binding sites in their 3′-untranslated regions. In these cells, the active Ser 2448-phosphorylated form of mTOR is present only in mitotic cells in association with the mitotic spindle and midbody in the G2-M phases of the cell cycle. Pharmacologic inhibition of mTOR signaling by everolimus greatly reduces tumor cell growth in vitro and in vivo. Our results reveal a novel mechanism of regulation of mTOR signaling by miRNAs, and they lay the groundwork for clinical evaluation of drugs inhibiting the mTOR pathway for treatment of adrenocortical cancer. ©2010 AACR.
Authors & Co-Authors
Doghman-Bouguerra, Mabrouka
France, Valbonne
Institut de Pharmacologie Moléculaire et Cellulaire
France, Nice
Université Côte D'azur
El Wakil, Abeer
France, Valbonne
Institut de Pharmacologie Moléculaire et Cellulaire
France, Nice
Université Côte D'azur
Lalli, Enzo
France, Valbonne
Institut de Pharmacologie Moléculaire et Cellulaire
France, Nice
Université Côte D'azur
Statistics
Citations: 182
Authors: 3
Affiliations: 5
Identifiers
Doi:
10.1158/0008-5472.CAN-09-3970
ISSN:
00085472
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health