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Coding-Independent Regulation of the Tumor Suppressor PTEN by Competing Endogenous mRNAs

2011; Cell Press; Volume: 147; Issue: 2 Linguagem: Inglês

10.1016/j.cell.2011.09.029

1097-4172

Yvonne Tay, Lev M. Kats, Leonardo Salmena, Dror Weiss, Shen Mynn Tan, Ugo Ala, Florian A. Karreth, Laura Poliseno, Paolo Provero, Ferdinando Di Cunto, Judy Lieberman, Isidore Rigoutsos, Pier Paolo Pandolfi,

PI3K/AKT/mTOR signaling in cancer

Here, we demonstrate that protein-coding RNA transcripts can crosstalk by competing for common microRNAs, with microRNA response elements as the foundation of this interaction. We have termed such RNA transcripts as competing endogenous RNAs (ceRNAs). We tested this hypothesis in the context of PTEN, a key tumor suppressor whose abundance determines critical outcomes in tumorigenesis. By a combined computational and experimental approach, we identified and validated endogenous protein-coding transcripts that regulate PTEN, antagonize PI3K/AKT signaling, and possess growth- and tumor-suppressive properties. Notably, we also show that these genes display concordant expression patterns with PTEN and copy number loss in cancers. Our study presents a road map for the prediction and validation of ceRNA activity and networks and thus imparts a trans-regulatory function to protein-coding mRNAs.