title: Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature.
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.
authors.affiliation: Center for Applied Medical Research, University of Navarra, 55 Pio XII Avenue, 31008 Pamplona, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Sánchez
authors.affiliation: Center for Applied Medical Research, University of Navarra, 55 Pio XII Avenue, 31008 Pamplona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Segura
authors.affiliation: Center for Applied Medical Research, University of Navarra, 55 Pio XII Avenue, 31008 Pamplona, Spain.
authors.forename: Oskar
authors.initials: O
authors.lastname: Marín-Béjar
authors.affiliation: Center for Applied Medical Research, University of Navarra, 55 Pio XII Avenue, 31008 Pamplona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Athie
authors.affiliation: Center for Applied Medical Research, University of Navarra, 55 Pio XII Avenue, 31008 Pamplona, Spain.
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Marchese
authors.affiliation: Center for Applied Medical Research, University of Navarra, 55 Pio XII Avenue, 31008 Pamplona, Spain.
authors.forename: Jovanna
authors.initials: J
authors.lastname: González
authors.affiliation: Department of Gastroenterology, 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, 20014 San Sebastian, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, California 92008, USA.
authors.forename: Shuling
authors.initials: S
authors.lastname: Guo
authors.affiliation: 1] Neuro-Oncology Section, Oncology Department, Biodonostia Research Institute, Dr Begiristain Square, 20014 San Sebastian, Spain [2] Ikerbasque, Basque Foundation for Science, Bilbao 48013, Spain.
authors.forename: Ander
authors.initials: A
authors.lastname: Matheu
authors.affiliation: Center for Applied Medical Research, University of Navarra, 55 Pio XII Avenue, 31008 Pamplona, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: Huarte
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D016147:Genes, Tumor Suppressor; D045325:HCT116 Cells; D006801:Humans; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53