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Oncogene. 2011 May 12;30(19):2242-51. doi: 10.1038/onc.2010.602. Epub 2011 Jan 17.

Myc/miR-378/TOB2/cyclin D1 functional module regulates oncogenic transformation.

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  • 1Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore.

Abstract

The c-Myc transcription factor activates a cascade of downstream targets to form a complex transcriptional program that ultimately leads to cellular transformation. Although a large number of protein-encoding genes as well as non-coding RNAs were identified as Myc targets, only a few have been validated to be functionally important for c-Myc-driven transformation. Here, we identify a microRNA (miRNA), miR-378, as a novel target of the c-Myc oncoprotein that is able to cooperate with activated Ras or HER2 to promote cellular transformation. Mechanistically, miR-378 achieves this oncogenic effect, at least in part, by targeting and inhibiting the anti-proliferative BTG family member, TOB2, which is further elucidated as a candidate tumor suppressor to transcriptionally repress proto-oncogene cyclin D1. Therefore, our study identifies miR-378-TOB2-cyclin D1 as a functional module to mediate the cross talk between Myc and Ras signaling in cellular transformation.

PMID:
21242960
[PubMed - indexed for MEDLINE]
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