Journal article
Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs
Y Tay, L Kats, L Salmena, D Weiss, SM Tan, U Ala, F Karreth, L Poliseno, P Provero, F Di Cunto, J Lieberman, I Rigoutsos, PP Pandolfi
Cell | CELL PRESS | Published : 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 PTE..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Pandolfi laboratory members for critical discussions. Real-time PCR analysis was conducted through the Harvard Catalyst Laboratory for Innovative Translational Technologies with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. We thank B. Vogelstein for DICER<SUP>Ex5</SUP> cells, M. Gorospe for the pMS2 plasmids, and I. Legnini for experimental support. Y.T. was supported by a Special Fellow Award from The Leukemia & Lymphoma Society. L. K. was supported by an NHMRC Overseas Postdoctoral Fellowship. L. S. was supported by fellowships from the Human Frontier Science Program and the Canadian Institutes of Health Research. U. A. was supported by a fellowship from the Fondazione per la Ricerca Biomedica ONLUS of Torino. S. M. T. was supported by a Department of Defense (DOD) Breast Cancer Research Program (BCRP) postdoctoral fellowship award. P. P. and U. A. gratefully acknowledge support from the Italian Association for Cancer Research (AIRC) under grant IG-9408. I. R. was supported by funding from the Jefferson Medical College of Thomas Jefferson University. This work was supported, in part, by NIH grant R01 CA-82328-09 to P.P.