title: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs.
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.
authors: Cancer Genetics Program, Division of Genetics, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Yvonne
authors: Y
authors: Tay
authors: Lev
authors: L
authors: Kats
authors: Leonardo
authors: L
authors: Salmena
authors: Dror
authors: D
authors: Weiss
authors: Shen Mynn
authors: SM
authors: Tan
authors: Ugo
authors: U
authors: Ala
authors: Florian
authors: F
authors: Karreth
authors: Laura
authors: L
authors: Poliseno
authors: Paolo
authors: P
authors: Provero
authors: Ferdinando
authors: F
authors: Di Cunto
authors: Judy
authors: J
authors: Lieberman
authors: Isidore
authors: I
authors: Rigoutsos
authors: Pier Paolo
authors: PP
authors: Pandolfi
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D022661:RNA, Untranslated; D038621:Regulatory Sequences, Ribonucleic Acid; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C487757:Pten protein, mouse