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American Association for Cancer Research, Cancer Research, 11(70), p. 4666-4675, 2010

DOI: 10.1158/0008-5472.can-09-3970

The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego, p. OR20-4-OR20-4

DOI: 10.1210/endo-meetings.2010.part3.or1.or20-4

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Regulation of Insulin-like Growth Factor–Mammalian Target of Rapamycin Signaling by MicroRNA in Childhood Adrenocortical Tumors

Journal article published in 2010 by Mabrouka Doghman, Abeer El Wakil ORCID, Bruno Cardinaud, Emilie Thomas, Jinling Wang, Wei Zhao, Maria Helena C. Peralta-Del Valle, Bonald C. Figueiredo ORCID, Gerard P. Zambetti, Enzo Lalli
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Abstract 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 Ser2448-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. Cancer Res; 70(11); 4666–75. ©2010 AACR.