Title: p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response
Authors: Aerts, Stein # ×
Hattori, H
Janky, R
Nietfeld, W
Madan Babu, A
Venkitaraman, A
Issue Date: 6-Jun-2014
Publisher: Landes Bioscience
Series Title: Cell Cycle
Abstract: 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.
ISSN: 1538-4101
Publication status: submitted
KU Leuven publication type: IT
Appears in Collections:Laboratory of Computational Biology
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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