A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?
Open accessAbstract
Here, we present a unifying hypothesis about how messenger RNAs, transcribed pseudogenes, and long noncoding RNAs "talk" to each other using microRNA response elements (MREs) as letters of a new language. We propose that this "competing endogenous RNA" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer.
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LncRNAs can share common miRNA binding sites of mRNAs, thereby blocking the binding of target mRNAs to miRNAs and abolishing the downstream effects of those miRNAs.
“Moreover, lncRNAs could share common miRNA binding sites of mRNAs, thus blocking the binding of target mRNAs to miRNAs and abolishing the downstream effects of these miRNAs25.”
From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [25]
The ceRNA hypothesis sections describe non-coding RNAs competing with mRNAs for shared microRNA binding and give an example of an lncRNA sequestering a microRNA (page numbers unavailable). They describe impaired microRNA activity and diluted repression, not complete blocking of microRNA binding to target mRNAs or abolition of its downstream effects. (LLM, conf=0.88)
Experimental — accuracy not yet measuredceRNAs, such as lncRNAs, compete for binding to miRNAs through miRNA response elements (MREs), preventing miRNA binding to target mRNAs.
“ceRNAs, such as lncRNAs, could compete for binding to miRNAs through miRNA response elements (MREs), thus preventing the binding of miRNAs to target mRNAs25.”
From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [25]
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- Authors
- Salmena, L., Poliseno, L., Tay, Y., Kats, L., & Pandolfi, P. P.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Pandolfi, Pier Paolo
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 146
- Issue
- 3
- Pages
- 353-358
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3235919
- OpenAlex
- W2046387002
- Cited by
- 7,262
- References
- 7
- Citations by year
- 2026: 306 · 2025: 392 · 2024: 567 · 2023: 683 · 2022: 968 · 2021: 1080 · 2020: 924 · 2019: 688 · 2018: 450 · 2017: 302 · 2016: 194 · 2015: 201 · 2014: 176 · 2013: 173 · 2012: 132
- FWCI
- 51.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- American-Italian Cancer Foundation
- Istituto Toscano Tumori
- National Institutes of Health
- Canadian Institutes of Health Research
- National Health and Medical Research Council
- National Cancer Institute (R01 CA-82328-09, R01CA082328)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- competing endogenous RNA, microRNA response elements, long non-coding RNA, pseudogenes, mRNA, cancer, gene expression regulation
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Neoplasms, Pseudogenes, RNA, RNA, Messenger, Gene Expression Profiling, RNA, Untranslated, MicroRNAs
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