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

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-05, Vol.70 (11), p.4666-4675
• Main Authors: Doghman, Mabrouka, Wakil, Abeer EL, Cardinaud, Bruno, Thomas, Emilie, Wang, Jinling, Zhao, Wei, Peralta-Del Valle, Maria Helena C., Figueiredo, Bonald C., Zambetti, Gerard P., Lalli, Enzo
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-09-3970

MicroRNAs (miRNAs) act at the post-transcriptional 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, including miR-99a and miR-100. Functional analysis of these miRNAs in adrenocortical tumor cell lines showed that they coordinately regulate expression of the IGF-mTOR-raptor signalling pathway through binding sites in their 3′ UTRs. 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. Pharmacological inhibition of mTOR signalling by everolimus greatly reduces tumor cell growth in vitro and in vivo. Our results reveal a novel mechanism of regulation of mTOR signalling by miRNAs, and they lay the groundwork for clinical evaluation of mTOR pathway drugs for treatment of adrenocortical cancer.