p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity - PubMed (original) (raw)
doi: 10.1038/nm.4135. Epub 2016 Jul 4.
Laura Standaert 1 2, Jasmine Barra 1 2, Mathilde Latil 3, Annelien Verfaillie 4, Peter Kalev 5 6, Bram Boeckx 7 8, Paul W G Wijnhoven 9, Enrico Radaelli 10, William Vermi 11 12, Eleonora Leucci 1 2, Gaëlle Lapouge 3, Benjamin Beck 3, Joost van den Oord 13, Shinichi Nakagawa 14 15, Tetsuro Hirose 16, Anna A Sablina 5 6, Diether Lambrechts 7 8, Stein Aerts 4, Cédric Blanpain 3 17, Jean-Christophe Marine 1 2
Affiliations
- PMID: 27376578
- DOI: 10.1038/nm.4135
p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity
Carmen Adriaens et al. Nat Med. 2016 Aug.
Erratum in
- Publisher Correction: p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity.
Adriaens C, Standaert L, Barra J, Latil M, Verfaillie A, Kalev P, Boeckx B, Wijnhoven PWG, Radaelli E, Vermi W, Leucci E, Lapouge G, Beck B, van den Oord J, Nakagawa S, Hirose T, Sablina AA, Lambrechts D, Aerts S, Blanpain C, Marine JC. Adriaens C, et al. Nat Med. 2024 May;30(5):1506. doi: 10.1038/s41591-024-02842-w. Nat Med. 2024. PMID: 38332041 No abstract available.
Abstract
In a search for mediators of the p53 tumor suppressor pathway, which induces pleiotropic and often antagonistic cellular responses, we identified the long noncoding RNA (lncRNA) NEAT1. NEAT1 is an essential architectural component of paraspeckle nuclear bodies, whose pathophysiological relevance remains unclear. Activation of p53, pharmacologically or by oncogene-induced replication stress, stimulated the formation of paraspeckles in mouse and human cells. Silencing Neat1 expression in mice, which prevents paraspeckle formation, sensitized preneoplastic cells to DNA-damage-induced cell death and impaired skin tumorigenesis. We provide mechanistic evidence that NEAT1 promotes ATR signaling in response to replication stress and is thereby engaged in a negative feedback loop that attenuates oncogene-dependent activation of p53. NEAT1 targeting in established human cancer cell lines induced synthetic lethality with genotoxic chemotherapeutics, including PARP inhibitors, and nongenotoxic activation of p53. This study establishes a key genetic link between NEAT1 paraspeckles, p53 biology and tumorigenesis and identifies NEAT1 as a promising target to enhance sensitivity of cancer cells to both chemotherapy and p53 reactivation therapy.
Similar articles
- Long non-coding RNA NEAT1 is a transcriptional target of p53 and modulates p53-induced transactivation and tumor-suppressor function.
Idogawa M, Ohashi T, Sasaki Y, Nakase H, Tokino T. Idogawa M, et al. Int J Cancer. 2017 Jun 15;140(12):2785-2791. doi: 10.1002/ijc.30689. Epub 2017 Mar 27. Int J Cancer. 2017. PMID: 28295289 - Hepatocellular Carcinoma and Nuclear Paraspeckles: Induction in Chemoresistance and Prediction for Poor Survival.
Kessler SM, Hosseini K, Hussein UK, Kim KM, List M, Schultheiß CS, Schulz MH, Laggai S, Jang KY, Kiemer AK. Kessler SM, et al. Cell Physiol Biochem. 2019;52(4):787-801. doi: 10.33594/000000055. Cell Physiol Biochem. 2019. PMID: 30946555 - Neat1 is a p53-inducible lincRNA essential for transformation suppression.
Mello SS, Sinow C, Raj N, Mazur PK, Bieging-Rolett K, Broz DK, Imam JFC, Vogel H, Wood LD, Sage J, Hirose T, Nakagawa S, Rinn J, Attardi LD. Mello SS, et al. Genes Dev. 2017 Jun 1;31(11):1095-1108. doi: 10.1101/gad.284661.116. Epub 2017 Jul 11. Genes Dev. 2017. PMID: 28698299 Free PMC article. - Neat-en-ing up our understanding of p53 pathways in tumor suppression.
Mello SS, Attardi LD. Mello SS, et al. Cell Cycle. 2018;17(13):1527-1535. doi: 10.1080/15384101.2018.1464835. Epub 2018 Jul 31. Cell Cycle. 2018. PMID: 29895201 Free PMC article. Review. - Molecular anatomy of the architectural NEAT1 noncoding RNA: The domains, interactors, and biogenesis pathway required to build phase-separated nuclear paraspeckles.
Hirose T, Yamazaki T, Nakagawa S. Hirose T, et al. Wiley Interdiscip Rev RNA. 2019 Nov;10(6):e1545. doi: 10.1002/wrna.1545. Epub 2019 May 1. Wiley Interdiscip Rev RNA. 2019. PMID: 31044562 Review.
Cited by
- Targeting mutant p53: a key player in breast cancer pathogenesis and beyond.
Qayoom H, Haq BU, Sofi S, Jan N, Jan A, Mir MA. Qayoom H, et al. Cell Commun Signal. 2024 Oct 10;22(1):484. doi: 10.1186/s12964-024-01863-9. Cell Commun Signal. 2024. PMID: 39390510 Free PMC article. Review. - NEAT1 modulates the TIRR/53BP1 complex to maintain genome integrity.
Kilgas S, Syed A, Toolan-Kerr P, Swift ML, Roychoudhury S, Sarkar A, Wilkins S, Quigley M, Poetsch AR, Botuyan MV, Cui G, Mer G, Ule J, Drané P, Chowdhury D. Kilgas S, et al. Nat Commun. 2024 Sep 30;15(1):8438. doi: 10.1038/s41467-024-52862-w. Nat Commun. 2024. PMID: 39349456 Free PMC article. - LncRNA NEAT1 and miRNA 101 as potential diagnostic biomarkers in patients with alopecia areata.
Erfan R, Shaker OG, Khalil MAF, Hassan AR, Abu-El-Azayem AK, Samy A, Abdelhamid H, Awaji AA, El Sayed HS, Mohammed A. Erfan R, et al. Noncoding RNA Res. 2024 Aug 14;10:35-40. doi: 10.1016/j.ncrna.2024.08.005. eCollection 2025 Feb. Noncoding RNA Res. 2024. PMID: 39296639 Free PMC article. - Multiple roles of arsenic compounds in phase separation and membraneless organelles formation determine their therapeutic efficacy in tumors.
Qu M, He Q, Bao H, Ji X, Shen T, Barkat MQ, Wu X, Zeng LH. Qu M, et al. J Pharm Anal. 2024 Aug;14(8):100957. doi: 10.1016/j.jpha.2024.02.011. Epub 2024 Feb 24. J Pharm Anal. 2024. PMID: 39253293 Free PMC article. Review. - ATR/Chk1 interacting lncRNA modulates DNA damage response to induce breast cancer chemoresistance.
Luo R, Wu J, Chen X, Liu Y, Liu D, Song E, Luo ML. Luo R, et al. Cell Insight. 2024 Jul 14;3(5):100183. doi: 10.1016/j.cellin.2024.100183. eCollection 2024 Oct. Cell Insight. 2024. PMID: 39148723 Free PMC article.
References
- Bioinformatics. 2015 Jan 15;31(2):166-9 - PubMed
- Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8551-6 - PubMed
- Genome Biol. 2013;14(9):R104 - PubMed
- Nucleic Acids Res. 2012 Aug;40(15):e114 - PubMed
- Front Biosci (Elite Ed). 2015 Jan 01;7:1-41 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous