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Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature

Author

Listed:
  • Yolanda Sánchez

    (Center for Applied Medical Research, University of Navarra)

  • Victor Segura

    (Center for Applied Medical Research, University of Navarra)

  • Oskar Marín-Béjar

    (Center for Applied Medical Research, University of Navarra)

  • Alejandro Athie

    (Center for Applied Medical Research, University of Navarra)

  • Francesco P. Marchese

    (Center for Applied Medical Research, University of Navarra)

  • Jovanna González

    (Center for Applied Medical Research, University of Navarra)

  • Luis Bujanda

    (Donostia Hospital—Biodonostia Research Institute, University of Basque Country (UPV/EHU), Biomedical Research Center in the Network of Digestive and Hepatic Diseases (CIBERehd), Dr Begiristain Square)

  • Shuling Guo

    (Isis Pharmaceuticals)

  • Ander Matheu

    (Neuro-Oncology Section, Biodonostia Research Institute, Dr Begiristain Square
    Ikerbasque, Basque Foundation for Science)

  • Maite Huarte

    (Center for Applied Medical Research, University of Navarra)

Abstract

Despite the inarguable relevance of p53 in cancer, genome-wide studies relating endogenous p53 activity to the expression of lncRNAs in human cells are still missing. Here, by integrating RNA-seq with p53 ChIP-seq analyses of a human cancer cell line under DNA damage, we define a high-confidence set of 18 lncRNAs that are p53 transcriptional targets. We demonstrate that two of the p53-regulated lncRNAs are required for the efficient binding of p53 to some of its target genes, modulating the p53 transcriptional network and contributing to apoptosis induction by DNA damage. We also show that the expression of p53-lncRNAs is lowered in colorectal cancer samples, constituting a tumour suppressor signature with high diagnostic power. Thus, p53-regulated lncRNAs establish a positive regulatory feedback loop that enhances p53 tumour suppressor activity. Furthermore, the signature defined by p53-regulated lncRNAs supports their potential use in the clinic as biomarkers and therapeutic targets.

Suggested Citation

  • Yolanda Sánchez & Victor Segura & Oskar Marín-Béjar & Alejandro Athie & Francesco P. Marchese & Jovanna González & Luis Bujanda & Shuling Guo & Ander Matheu & Maite Huarte, 2014. "Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6812
    DOI: 10.1038/ncomms6812
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    Cited by:

    1. Olga Boix & Marion Martinez & Santiago Vidal & Marta Giménez-Alejandre & Lluís Palenzuela & Laura Lorenzo-Sanz & Laura Quevedo & Olivier Moscoso & Jorge Ruiz-Orera & Pilar Ximénez-Embún & Nikaoly Ciri, 2022. "pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    2. Lingxiang Wu & Xiujie Chen & Denan Zhang & Wubing Zhang & Lei Liu & Hongzhe Ma & Jingbo Yang & Hongbo Xie & Bo Liu & Qing Jin, 2016. "IGSA: Individual Gene Sets Analysis, including Enrichment and Clustering," PLOS ONE, Public Library of Science, vol. 11(10), pages 1-16, October.
    3. Luisa Statello & José Miguel Fernandez-Justel & Jovanna González & Marta Montes & Alessia Ranieri & Enrique Goñi & Aina M. Mas & Maite Huarte, 2024. "The chromatin-associated lncREST ensures effective replication stress response by promoting the assembly of fork signaling factors," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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