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p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response

The human DNA damage response (DDR) triggers profound changes in gene expression, whose nature and regulation remain uncertain. Although certain micro-(mi)RNA species including miR34, miR-18, miR-16 and miR-143 have been implicated in the DDR, there is as yet no comprehensive description of genome-w...

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Autores principales: Hattori, Hiroyoshi, Janky, Rekin’s, Nietfeld, Wilfried, Aerts, Stein, Madan Babu, M, Venkitaraman, Ashok R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601526/
https://www.ncbi.nlm.nih.gov/pubmed/25486198
http://dx.doi.org/10.4161/15384101.2015.942209
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author Hattori, Hiroyoshi
Janky, Rekin’s
Nietfeld, Wilfried
Aerts, Stein
Madan Babu, M
Venkitaraman, Ashok R
author_facet Hattori, Hiroyoshi
Janky, Rekin’s
Nietfeld, Wilfried
Aerts, Stein
Madan Babu, M
Venkitaraman, Ashok R
author_sort Hattori, Hiroyoshi
collection PubMed
description The human DNA damage response (DDR) triggers profound changes in gene expression, whose nature and regulation remain uncertain. Although certain micro-(mi)RNA species including miR34, miR-18, miR-16 and miR-143 have been implicated in the DDR, there is as yet no comprehensive description of genome-wide changes in the expression of miRNAs triggered by DNA breakage in human cells. We have used next-generation sequencing (NGS), combined with rigorous integrative computational analyses, to describe genome-wide changes in the expression of miRNAs during the human DDR. The changes affect 150 of 1523 miRNAs known in miRBase v18 from 4–24 h after the induction of DNA breakage, in cell-type dependent patterns. The regulatory regions of the most-highly regulated miRNA species are enriched in conserved binding sites for p53. Indeed, genome-wide changes in miRNA expression during the DDR are markedly altered in TP53-/- cells compared to otherwise isogenic controls. The expression levels of certain damage-induced, p53-regulated miRNAs in cancer samples correlate with patient survival. Our work reveals genome-wide and cell type-specific alterations in miRNA expression during the human DDR, which are regulated by the tumor suppressor protein p53. These findings provide a genomic resource to identify new molecules and mechanisms involved in the DDR, and to examine their role in tumor suppression and the clinical outcome of cancer patients.
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spelling pubmed-46015262015-10-12 p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response Hattori, Hiroyoshi Janky, Rekin’s Nietfeld, Wilfried Aerts, Stein Madan Babu, M Venkitaraman, Ashok R Cell Cycle Report The human DNA damage response (DDR) triggers profound changes in gene expression, whose nature and regulation remain uncertain. Although certain micro-(mi)RNA species including miR34, miR-18, miR-16 and miR-143 have been implicated in the DDR, there is as yet no comprehensive description of genome-wide changes in the expression of miRNAs triggered by DNA breakage in human cells. We have used next-generation sequencing (NGS), combined with rigorous integrative computational analyses, to describe genome-wide changes in the expression of miRNAs during the human DDR. The changes affect 150 of 1523 miRNAs known in miRBase v18 from 4–24 h after the induction of DNA breakage, in cell-type dependent patterns. The regulatory regions of the most-highly regulated miRNA species are enriched in conserved binding sites for p53. Indeed, genome-wide changes in miRNA expression during the DDR are markedly altered in TP53-/- cells compared to otherwise isogenic controls. The expression levels of certain damage-induced, p53-regulated miRNAs in cancer samples correlate with patient survival. Our work reveals genome-wide and cell type-specific alterations in miRNA expression during the human DDR, which are regulated by the tumor suppressor protein p53. These findings provide a genomic resource to identify new molecules and mechanisms involved in the DDR, and to examine their role in tumor suppression and the clinical outcome of cancer patients. Taylor & Francis 2014-10-30 /pmc/articles/PMC4601526/ /pubmed/25486198 http://dx.doi.org/10.4161/15384101.2015.942209 Text en © 2014 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Report
Hattori, Hiroyoshi
Janky, Rekin’s
Nietfeld, Wilfried
Aerts, Stein
Madan Babu, M
Venkitaraman, Ashok R
p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response
title p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response
title_full p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response
title_fullStr p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response
title_full_unstemmed p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response
title_short p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response
title_sort p53 shapes genome-wide and cell type-specific changes in microrna expression during the human dna damage response
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601526/
https://www.ncbi.nlm.nih.gov/pubmed/25486198
http://dx.doi.org/10.4161/15384101.2015.942209
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