SLUG/HIF1-α/miR-221 regulatory circuit in endometrial cancer.
Aged
Aged, 80 and over
Body Mass Index
Endometrial Neoplasms
/ genetics
Estrogen Receptor alpha
/ metabolism
Female
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
MicroRNAs
/ genetics
Middle Aged
Obesity
/ genetics
Receptors, Progesterone
/ metabolism
Retrospective Studies
Risk Factors
Snail Family Transcription Factors
/ genetics
Tumor Microenvironment
Endometrial cancer
Estrogen receptor
HIF1-α
Obesity
SLUG
miR-221
Journal
Gene
ISSN: 1879-0038
Titre abrégé: Gene
Pays: Netherlands
ID NLM: 7706761
Informations de publication
Date de publication:
30 Aug 2019
30 Aug 2019
Historique:
received:
05
03
2019
revised:
13
06
2019
accepted:
17
06
2019
pubmed:
21
6
2019
medline:
30
7
2019
entrez:
21
6
2019
Statut:
ppublish
Résumé
The pathogenesis of endometrial cancer (EC) involves many regulatory pathways including transcriptional regulatory networks supported by transcription factors and microRNAs only in part known. The aim of this retrospective study was to explore the possible correlation in the EC microenvironment between master regulators of complex phenomena such as steroid responsiveness through estrogen receptor alpha (ERα) and progesterone receptor (PR), epithelial-to-mesenchymal transition (supported by SLUG transcription factor), hypoxia (with hypoxia inducible factor-1 alpha, HIF-1α), and obesity that has been recognized as a EC risk factor. Formalin-Fixed Paraffin-Embedded (FFPE) blocks from University of Ferrara Pathology Archive were used and allocated into 2 groups according to their immunohistochemical positivity to ERα and PR, distinguishing the samples with a more benign prognosis (ERα We showed a comparable percentage of HIF1-α and SLUG positive samples in the ERα A molecular circuit of mutual regulation between ERα, PR, HIF1-α, SLUG and miR-221 is feasible in the EC and was firstly suggested by our research. In this interplay miR-221 seems to be in a nodal point of the regulatory system that is particularly strengthened by the metabolic changes in obesity.
Sections du résumé
BACKGROUND AND PURPOSE
OBJECTIVE
The pathogenesis of endometrial cancer (EC) involves many regulatory pathways including transcriptional regulatory networks supported by transcription factors and microRNAs only in part known. The aim of this retrospective study was to explore the possible correlation in the EC microenvironment between master regulators of complex phenomena such as steroid responsiveness through estrogen receptor alpha (ERα) and progesterone receptor (PR), epithelial-to-mesenchymal transition (supported by SLUG transcription factor), hypoxia (with hypoxia inducible factor-1 alpha, HIF-1α), and obesity that has been recognized as a EC risk factor.
METHODS
METHODS
Formalin-Fixed Paraffin-Embedded (FFPE) blocks from University of Ferrara Pathology Archive were used and allocated into 2 groups according to their immunohistochemical positivity to ERα and PR, distinguishing the samples with a more benign prognosis (ERα
RESULTS
RESULTS
We showed a comparable percentage of HIF1-α and SLUG positive samples in the ERα
CONCLUSIONS
CONCLUSIONS
A molecular circuit of mutual regulation between ERα, PR, HIF1-α, SLUG and miR-221 is feasible in the EC and was firstly suggested by our research. In this interplay miR-221 seems to be in a nodal point of the regulatory system that is particularly strengthened by the metabolic changes in obesity.
Identifiants
pubmed: 31220580
pii: S0378-1119(19)30588-8
doi: 10.1016/j.gene.2019.06.028
pii:
doi:
Substances chimiques
ESR1 protein, human
0
Estrogen Receptor alpha
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
MIRN221 microRNA, human
0
MicroRNAs
0
Receptors, Progesterone
0
SNAI1 protein, human
0
Snail Family Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Pagination
143938Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.