Cargando…

miR-9-Mediated Inhibition of EFEMP1 Contributes to the Acquisition of Pro-Tumoral Properties in Normal Fibroblasts

Tumor growth and invasion occurs through a dynamic interaction between cancer and stromal cells, which support an aggressive niche. MicroRNAs are thought to act as tumor messengers to “corrupt” stromal cells. We previously demonstrated that miR-9, a known metastamiR, is released by triple negative b...

Descripción completa

Detalles Bibliográficos
Autores principales: Cosentino, Giulia, Romero-Cordoba, Sandra, Plantamura, Ilaria, Cataldo, Alessandra, Iorio, Marilena V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565260/
https://www.ncbi.nlm.nih.gov/pubmed/32972039
http://dx.doi.org/10.3390/cells9092143
_version_ 1783595894734585856
author Cosentino, Giulia
Romero-Cordoba, Sandra
Plantamura, Ilaria
Cataldo, Alessandra
Iorio, Marilena V.
author_facet Cosentino, Giulia
Romero-Cordoba, Sandra
Plantamura, Ilaria
Cataldo, Alessandra
Iorio, Marilena V.
author_sort Cosentino, Giulia
collection PubMed
description Tumor growth and invasion occurs through a dynamic interaction between cancer and stromal cells, which support an aggressive niche. MicroRNAs are thought to act as tumor messengers to “corrupt” stromal cells. We previously demonstrated that miR-9, a known metastamiR, is released by triple negative breast cancer (TNBC) cells to enhance the transition of normal fibroblasts (NFs) into cancer-associated fibroblast (CAF)-like cells. EGF containing fibulin extracellular matrix protein 1 (EFEMP1), which encodes for the ECM glycoprotein fibulin-3, emerged as a miR-9 putative target upon miRNA’s exogenous upmodulation in NFs. Here we explored the impact of EFEMP1 downmodulation on fibroblast’s acquisition of CAF-like features, and how this phenotype influences neoplastic cells to gain chemoresistance. Indeed, upon miR-9 overexpression in NFs, EFEMP1 resulted downmodulated, both at RNA and protein levels. The luciferase reporter assay showed that miR-9 directly targets EFEMP1 and its silencing recapitulates miR-9-induced pro-tumoral phenotype in fibroblasts. In particular, EFEMP1 siRNA-transfected (si-EFEMP1) fibroblasts have an increased ability to migrate and invade. Moreover, TNBC cells conditioned with the supernatant of NFs transfected with miR-9 or si-EFEMP1 became more resistant to cisplatin. Overall, our results demonstrate that miR-9/EFEMP1 axis is crucial for the conversion of NFs to CAF-like cells under TNBC signaling.
format Online
Article
Text
id pubmed-7565260
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75652602020-10-26 miR-9-Mediated Inhibition of EFEMP1 Contributes to the Acquisition of Pro-Tumoral Properties in Normal Fibroblasts Cosentino, Giulia Romero-Cordoba, Sandra Plantamura, Ilaria Cataldo, Alessandra Iorio, Marilena V. Cells Article Tumor growth and invasion occurs through a dynamic interaction between cancer and stromal cells, which support an aggressive niche. MicroRNAs are thought to act as tumor messengers to “corrupt” stromal cells. We previously demonstrated that miR-9, a known metastamiR, is released by triple negative breast cancer (TNBC) cells to enhance the transition of normal fibroblasts (NFs) into cancer-associated fibroblast (CAF)-like cells. EGF containing fibulin extracellular matrix protein 1 (EFEMP1), which encodes for the ECM glycoprotein fibulin-3, emerged as a miR-9 putative target upon miRNA’s exogenous upmodulation in NFs. Here we explored the impact of EFEMP1 downmodulation on fibroblast’s acquisition of CAF-like features, and how this phenotype influences neoplastic cells to gain chemoresistance. Indeed, upon miR-9 overexpression in NFs, EFEMP1 resulted downmodulated, both at RNA and protein levels. The luciferase reporter assay showed that miR-9 directly targets EFEMP1 and its silencing recapitulates miR-9-induced pro-tumoral phenotype in fibroblasts. In particular, EFEMP1 siRNA-transfected (si-EFEMP1) fibroblasts have an increased ability to migrate and invade. Moreover, TNBC cells conditioned with the supernatant of NFs transfected with miR-9 or si-EFEMP1 became more resistant to cisplatin. Overall, our results demonstrate that miR-9/EFEMP1 axis is crucial for the conversion of NFs to CAF-like cells under TNBC signaling. MDPI 2020-09-22 /pmc/articles/PMC7565260/ /pubmed/32972039 http://dx.doi.org/10.3390/cells9092143 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cosentino, Giulia
Romero-Cordoba, Sandra
Plantamura, Ilaria
Cataldo, Alessandra
Iorio, Marilena V.
miR-9-Mediated Inhibition of EFEMP1 Contributes to the Acquisition of Pro-Tumoral Properties in Normal Fibroblasts
title miR-9-Mediated Inhibition of EFEMP1 Contributes to the Acquisition of Pro-Tumoral Properties in Normal Fibroblasts
title_full miR-9-Mediated Inhibition of EFEMP1 Contributes to the Acquisition of Pro-Tumoral Properties in Normal Fibroblasts
title_fullStr miR-9-Mediated Inhibition of EFEMP1 Contributes to the Acquisition of Pro-Tumoral Properties in Normal Fibroblasts
title_full_unstemmed miR-9-Mediated Inhibition of EFEMP1 Contributes to the Acquisition of Pro-Tumoral Properties in Normal Fibroblasts
title_short miR-9-Mediated Inhibition of EFEMP1 Contributes to the Acquisition of Pro-Tumoral Properties in Normal Fibroblasts
title_sort mir-9-mediated inhibition of efemp1 contributes to the acquisition of pro-tumoral properties in normal fibroblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565260/
https://www.ncbi.nlm.nih.gov/pubmed/32972039
http://dx.doi.org/10.3390/cells9092143
work_keys_str_mv AT cosentinogiulia mir9mediatedinhibitionofefemp1contributestotheacquisitionofprotumoralpropertiesinnormalfibroblasts
AT romerocordobasandra mir9mediatedinhibitionofefemp1contributestotheacquisitionofprotumoralpropertiesinnormalfibroblasts
AT plantamurailaria mir9mediatedinhibitionofefemp1contributestotheacquisitionofprotumoralpropertiesinnormalfibroblasts
AT cataldoalessandra mir9mediatedinhibitionofefemp1contributestotheacquisitionofprotumoralpropertiesinnormalfibroblasts
AT ioriomarilenav mir9mediatedinhibitionofefemp1contributestotheacquisitionofprotumoralpropertiesinnormalfibroblasts