The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
PintlincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
Open accessAbstract
Background: The p53 transcription factor is located at the core of a complex wiring of signaling pathways that are critical for the preservation of cellular homeostasis. Only recently it has become clear that p53 regulates the expression of several long intergenic noncoding RNAs (lincRNAs). However, relatively little is known about the role that lincRNAs play in this pathway. Results: Here we characterize a lincRNA named Pint (p53 induced noncoding transcript). We show that Pint is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, Pint promotes cell proliferation and survival by regulating the expression of genes of the TGF-β, MAPK and p53 pathways. Pint is a nuclear lincRNA that directly interacts with the Polycomb repressive complex 2 (PRC2), and is required for PRC2 targeting of specific genes for H3K27 tri-methylation and repression. Furthermore, Pint functional activity is highly dependent on PRC2 expression. We have also identified Pint human ortholog (PINT), which presents suggestive analogies with the murine lincRNA. PINT is similarly regulated by p53, and its expression significantly correlates with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, PINT is downregulated in colon primary tumors, while its overexpression inhibits the proliferation of tumor cells, suggesting a possible role as tumor suppressor. Conclusions: Our results reveal a p53 autoregulatory negative mechanism where a lincRNA connects p53 activation with epigenetic silencing by PRC2. Additionally, we show analogies and differences between the murine and human orthologs, identifying a novel tumor suppressor candidate lincRNA.
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Cites
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“In fact, this has been shown for the lincRNA HOTAIR, which interacts with the PRC2 and Lysine-specific demethylase 1 complexes [41].”
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Cited by
The emerging role of lncRNAs in cancer
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Self-citationCensus and evaluation of p53 target genes
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Metadata
- Authors
- Marín-Béjar, O., Marchese, F. P., Athie, A., Sánchez, Y., González, J., Segura, V., Huang, L., Moreno, I., Navarro, A., Monzó, M., García-Foncillas, J., Rinn, J. L., Guo, S., & Huarte, M.
- Venue
- Genome Biology
- Published
- 2013-09-26
- Volume
- 14
- Issue
- 9
- Pages
- R104-R104
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- OpenAlex
- W2147985894
- Cited by
- 265
- References
- 45
- FWCI
- 6.93
- Type
- journal article
- Language
- en
- Open access
- gold
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- Marín-Béjar, O., Marchese, F. P., Athie, A., Sánchez, Y., González, J., Segura, V., Huang, L., Moreno, I., Navarro, A., Monzó, M., García-Foncillas, J., Rinn, J. L., Guo, S., & Huarte, M. (2013). PintlincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2. Genome Biology. https://doi.org/10.1186/gb-2013-14-9-r104
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