MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer: The hOrmone and Diet in the ETiology of breast cancer prospective study

Paola Muti, Sara Donzelli, Andrea Sacconi, Ahmed Hossain, Federica Ganci, Tania Frixa, Sabina Sieri, Vittorio Krogh, Franco Berrino, Francesca Biagioni, Sabrina Strano, Joseph Beyene, Yosef Yarden, Giovanni Blandino

Research output: Contribution to journalArticle

Abstract

report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR- 513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95% CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk.

Original languageEnglish
Pages (from-to)98-108
Number of pages11
JournalCarcinogenesis
Volume39
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Fingerprint

Progesterone Receptors
MicroRNAs
Hormones
Prospective Studies
Breast Neoplasms
Diet
Leukocytes
Up-Regulation
Biomarkers
Progesterone
Testosterone
Case-Control Studies
Cohort Studies
Multivariate Analysis
Serum

ASJC Scopus subject areas

  • Cancer Research

Cite this

MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer : The hOrmone and Diet in the ETiology of breast cancer prospective study. / Muti, Paola; Donzelli, Sara; Sacconi, Andrea; Hossain, Ahmed; Ganci, Federica; Frixa, Tania; Sieri, Sabina; Krogh, Vittorio; Berrino, Franco; Biagioni, Francesca; Strano, Sabrina; Beyene, Joseph; Yarden, Yosef; Blandino, Giovanni.

In: Carcinogenesis, Vol. 39, No. 2, 01.02.2018, p. 98-108.

Research output: Contribution to journalArticle

Muti, P, Donzelli, S, Sacconi, A, Hossain, A, Ganci, F, Frixa, T, Sieri, S, Krogh, V, Berrino, F, Biagioni, F, Strano, S, Beyene, J, Yarden, Y & Blandino, G 2018, 'MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer: The hOrmone and Diet in the ETiology of breast cancer prospective study', Carcinogenesis, vol. 39, no. 2, pp. 98-108. https://doi.org/10.1093/carcin/bgx126
Muti, Paola ; Donzelli, Sara ; Sacconi, Andrea ; Hossain, Ahmed ; Ganci, Federica ; Frixa, Tania ; Sieri, Sabina ; Krogh, Vittorio ; Berrino, Franco ; Biagioni, Francesca ; Strano, Sabrina ; Beyene, Joseph ; Yarden, Yosef ; Blandino, Giovanni. / MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer : The hOrmone and Diet in the ETiology of breast cancer prospective study. In: Carcinogenesis. 2018 ; Vol. 39, No. 2. pp. 98-108.
@article{991fff22783647798722b80589c605ae,
title = "MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer: The hOrmone and Diet in the ETiology of breast cancer prospective study",
abstract = "report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR- 513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95{\%} CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk.",
author = "Paola Muti and Sara Donzelli and Andrea Sacconi and Ahmed Hossain and Federica Ganci and Tania Frixa and Sabina Sieri and Vittorio Krogh and Franco Berrino and Francesca Biagioni and Sabrina Strano and Joseph Beyene and Yosef Yarden and Giovanni Blandino",
year = "2018",
month = "2",
day = "1",
doi = "10.1093/carcin/bgx126",
language = "English",
volume = "39",
pages = "98--108",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer

T2 - The hOrmone and Diet in the ETiology of breast cancer prospective study

AU - Muti, Paola

AU - Donzelli, Sara

AU - Sacconi, Andrea

AU - Hossain, Ahmed

AU - Ganci, Federica

AU - Frixa, Tania

AU - Sieri, Sabina

AU - Krogh, Vittorio

AU - Berrino, Franco

AU - Biagioni, Francesca

AU - Strano, Sabrina

AU - Beyene, Joseph

AU - Yarden, Yosef

AU - Blandino, Giovanni

PY - 2018/2/1

Y1 - 2018/2/1

N2 - report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR- 513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95% CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk.

AB - report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR- 513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95% CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk.

UR - http://www.scopus.com/inward/record.url?scp=85044455156&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044455156&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgx126

DO - 10.1093/carcin/bgx126

M3 - Article

AN - SCOPUS:85044455156

VL - 39

SP - 98

EP - 108

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 2

ER -