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Regulation of IGF - mTOR signalling by miRNA in childhood adrenocortical tumors

Doghman, Mabrouka and Wakil, Abeer EL and Cardinaud, Bruno and Thomas, Emilie and Wang, Jinling and Zhao, Wei and Figueiredo, Bonald C and Zambetti, Gerard P and Lalli, Enzo and Imark, Esther (2010) Regulation of IGF - mTOR signalling by miRNA in childhood adrenocortical tumors. Cancer Research, 70 (11). pp. 4666-4675. ISSN 0008-5472

Abstract

MicroRNAs belong to a class of small noncoding RNAs that control gene expression at the post-transcriptional level and are involved in virtually every biological process, including oncogenesis. Here we have identified a distinct set of miRNAs that are significantly regulated in adrenocortical tumors compared to normal adrenal cortex, including miR-99a and miR-100, which share the same seed sequence. Functional
analysis of the function of these miRNAs in adrenocortical tumor cell lines showed that they coordinately regulate expression of key components of the IGF – mTOR signalling
pathway (IGF-1R, mTOR and raptor) through binding sites in their 3' UTRs. In addition, we show that pharmacological inhibition of mTOR signalling greatly reduces adrenocortical tumor cell growth in vitro and in vivo. These data reveal a new mechanism of regulation of IGF – mTOR signalling by miRNAs and lay the groundwork for clinical experimentation of drugs targeting mTOR in the therapy of adrenocortical
cancer.

Item Type: Article
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/1605

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