Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs.
Publication/Presentation Date
10-14-2011
Abstract
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.
Volume
147
Issue
2
First Page
344
Last Page
357
ISSN
1097-4172
Published In/Presented At
Tay, Y., Kats, L., Salmena, L., Weiss, D., Tan, S. M., Ala, U., Karreth, F., Poliseno, L., Provero, P., Di Cunto, F., Lieberman, J., Rigoutsos, I., & Pandolfi, P. P. (2011). Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell, 147(2), 344–357. https://doi.org/10.1016/j.cell.2011.09.029
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
22000013
Department(s)
Administration and Leadership
Document Type
Article