Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs
By Yvonne Tay, Lev M. Kats, L. Salmena, Dror Weiss, S. Tan, U. Ala, F. Karreth, L. Poliseno, P. Provero, F. Di Cunto and 3 more. Cell, 2011
1,009 citations recorded by the source corpus.
SUMMARY 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.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/759e7f61604be3e0266e2b95545425f4ead2494b
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In Cancer Research
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In Molecular Biology
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Citations in the corpus
- TSGene 2.0: an updated literature-based knowledgebase for tumor suppressor genes (2015, background): “The inactivation or reduced function of protein-coding TSGs can be induced in many ways including promoter methylation changes (4), copy number alterations (5), deregulated mRNA expression due to microRNA (miRNA) activities (6) and competing endogenous long non-coding RNAs (lncRNAs) (7).”
- Roles for microRNAs in conferring robustness to biological processes. (2012, neutral): “…30 UTRs with more miRNA-binding sites (Stark et al., 2005); (2) miRNA expression increases and diversifies over the course of embryonic development (Thomson et al., 2006), as 30 UTRs are lengthened via alternative polyadenylation site choice (Ji et al., 2009); and (3) the diversity of the miRNA…”
- starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data (2013, background): “0, e.g. PTEN ceRNA: DCBLD2 ( P < 0.001), JARID2 ( P < 0.005), LRCH1 ( P < 0.00005), TNRC6A ( P < 0.00005) (12–14).”