Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer

Andrea Bisso, Michela Faleschini, Federico Zampa, Valeria Capaci, Jacopo De Santa, Libero Santapia, Silvano Piazza, Vera Cappelletti, Mariagrazia Daidone, Reuven Agami, Giannino Del Sal

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Breast cancer is a heterogeneous tumor type characterized by a complex spectrum of molecular aberrations, resulting in a diverse array of malignant features and clinical outcomes. Deciphering the molecular mechanisms that fuel breast cancer development and act as determinants of aggressiveness is a primary need to improve patient management. Among other alterations, aberrant expression of microRNAs has been found in breast cancer and other human tumors, where they act as either oncogenes or tumor suppressors by virtue of their ability to finely modulate gene expression at the post-transcriptional level. In this study, we describe a new role for miR-181a/b as negative regulators of the DNA damage response in breast cancer, impacting on the expression and activity of the stress-sensor kinase ataxia telangiectasia mutated (ATM). We report that miR-181a and miR-181b were overexpressed in more aggressive breast cancers, and their expression correlates inversely with ATM levels. Moreover we demonstrate that deregulated expression of miR-181a/b determines the sensitivity of triple-negative breast cancer cells to the poly-ADP-ribose-polymerase1 (PARP1) inhibition. These evidences suggest that monitoring the expression of miR-181a/b could be helpful in tailoring more effective treatments based on inhibition of PARP1 in breast and other tumor types.

Original languageEnglish
Pages (from-to)1679-1687
Number of pages9
JournalCell Cycle
Volume12
Issue number11
DOIs
Publication statusPublished - Jun 1 2013

Fingerprint

DNA Damage
Breast Neoplasms
Poly Adenosine Diphosphate Ribose
Ataxia Telangiectasia
Triple Negative Breast Neoplasms
Neoplasms
MicroRNAs
Oncogenes
Phosphotransferases
Gene Expression

Keywords

  • ATM
  • BRCA1
  • BRCAness
  • Breast cancer
  • DNA damage response
  • MicroRNA
  • PARP inhibitors

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Bisso, A., Faleschini, M., Zampa, F., Capaci, V., Santa, J. D., Santapia, L., ... Del Sal, G. (2013). Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer. Cell Cycle, 12(11), 1679-1687. https://doi.org/10.4161/cc.24757

Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer. / Bisso, Andrea; Faleschini, Michela; Zampa, Federico; Capaci, Valeria; Santa, Jacopo De; Santapia, Libero; Piazza, Silvano; Cappelletti, Vera; Daidone, Mariagrazia; Agami, Reuven; Del Sal, Giannino.

In: Cell Cycle, Vol. 12, No. 11, 01.06.2013, p. 1679-1687.

Research output: Contribution to journalArticle

Bisso, A, Faleschini, M, Zampa, F, Capaci, V, Santa, JD, Santapia, L, Piazza, S, Cappelletti, V, Daidone, M, Agami, R & Del Sal, G 2013, 'Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer', Cell Cycle, vol. 12, no. 11, pp. 1679-1687. https://doi.org/10.4161/cc.24757
Bisso A, Faleschini M, Zampa F, Capaci V, Santa JD, Santapia L et al. Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer. Cell Cycle. 2013 Jun 1;12(11):1679-1687. https://doi.org/10.4161/cc.24757
Bisso, Andrea ; Faleschini, Michela ; Zampa, Federico ; Capaci, Valeria ; Santa, Jacopo De ; Santapia, Libero ; Piazza, Silvano ; Cappelletti, Vera ; Daidone, Mariagrazia ; Agami, Reuven ; Del Sal, Giannino. / Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer. In: Cell Cycle. 2013 ; Vol. 12, No. 11. pp. 1679-1687.
@article{d569688de4014e13993dae753bcefdfa,
title = "Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer",
abstract = "Breast cancer is a heterogeneous tumor type characterized by a complex spectrum of molecular aberrations, resulting in a diverse array of malignant features and clinical outcomes. Deciphering the molecular mechanisms that fuel breast cancer development and act as determinants of aggressiveness is a primary need to improve patient management. Among other alterations, aberrant expression of microRNAs has been found in breast cancer and other human tumors, where they act as either oncogenes or tumor suppressors by virtue of their ability to finely modulate gene expression at the post-transcriptional level. In this study, we describe a new role for miR-181a/b as negative regulators of the DNA damage response in breast cancer, impacting on the expression and activity of the stress-sensor kinase ataxia telangiectasia mutated (ATM). We report that miR-181a and miR-181b were overexpressed in more aggressive breast cancers, and their expression correlates inversely with ATM levels. Moreover we demonstrate that deregulated expression of miR-181a/b determines the sensitivity of triple-negative breast cancer cells to the poly-ADP-ribose-polymerase1 (PARP1) inhibition. These evidences suggest that monitoring the expression of miR-181a/b could be helpful in tailoring more effective treatments based on inhibition of PARP1 in breast and other tumor types.",
keywords = "ATM, BRCA1, BRCAness, Breast cancer, DNA damage response, MicroRNA, PARP inhibitors",
author = "Andrea Bisso and Michela Faleschini and Federico Zampa and Valeria Capaci and Santa, {Jacopo De} and Libero Santapia and Silvano Piazza and Vera Cappelletti and Mariagrazia Daidone and Reuven Agami and {Del Sal}, Giannino",
year = "2013",
month = "6",
day = "1",
doi = "10.4161/cc.24757",
language = "English",
volume = "12",
pages = "1679--1687",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "11",

}

TY - JOUR

T1 - Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer

AU - Bisso, Andrea

AU - Faleschini, Michela

AU - Zampa, Federico

AU - Capaci, Valeria

AU - Santa, Jacopo De

AU - Santapia, Libero

AU - Piazza, Silvano

AU - Cappelletti, Vera

AU - Daidone, Mariagrazia

AU - Agami, Reuven

AU - Del Sal, Giannino

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Breast cancer is a heterogeneous tumor type characterized by a complex spectrum of molecular aberrations, resulting in a diverse array of malignant features and clinical outcomes. Deciphering the molecular mechanisms that fuel breast cancer development and act as determinants of aggressiveness is a primary need to improve patient management. Among other alterations, aberrant expression of microRNAs has been found in breast cancer and other human tumors, where they act as either oncogenes or tumor suppressors by virtue of their ability to finely modulate gene expression at the post-transcriptional level. In this study, we describe a new role for miR-181a/b as negative regulators of the DNA damage response in breast cancer, impacting on the expression and activity of the stress-sensor kinase ataxia telangiectasia mutated (ATM). We report that miR-181a and miR-181b were overexpressed in more aggressive breast cancers, and their expression correlates inversely with ATM levels. Moreover we demonstrate that deregulated expression of miR-181a/b determines the sensitivity of triple-negative breast cancer cells to the poly-ADP-ribose-polymerase1 (PARP1) inhibition. These evidences suggest that monitoring the expression of miR-181a/b could be helpful in tailoring more effective treatments based on inhibition of PARP1 in breast and other tumor types.

AB - Breast cancer is a heterogeneous tumor type characterized by a complex spectrum of molecular aberrations, resulting in a diverse array of malignant features and clinical outcomes. Deciphering the molecular mechanisms that fuel breast cancer development and act as determinants of aggressiveness is a primary need to improve patient management. Among other alterations, aberrant expression of microRNAs has been found in breast cancer and other human tumors, where they act as either oncogenes or tumor suppressors by virtue of their ability to finely modulate gene expression at the post-transcriptional level. In this study, we describe a new role for miR-181a/b as negative regulators of the DNA damage response in breast cancer, impacting on the expression and activity of the stress-sensor kinase ataxia telangiectasia mutated (ATM). We report that miR-181a and miR-181b were overexpressed in more aggressive breast cancers, and their expression correlates inversely with ATM levels. Moreover we demonstrate that deregulated expression of miR-181a/b determines the sensitivity of triple-negative breast cancer cells to the poly-ADP-ribose-polymerase1 (PARP1) inhibition. These evidences suggest that monitoring the expression of miR-181a/b could be helpful in tailoring more effective treatments based on inhibition of PARP1 in breast and other tumor types.

KW - ATM

KW - BRCA1

KW - BRCAness

KW - Breast cancer

KW - DNA damage response

KW - MicroRNA

KW - PARP inhibitors

UR - http://www.scopus.com/inward/record.url?scp=84878523316&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878523316&partnerID=8YFLogxK

U2 - 10.4161/cc.24757

DO - 10.4161/cc.24757

M3 - Article

VL - 12

SP - 1679

EP - 1687

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 11

ER -