Cargando…

Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, representing the most aggressive breast cancer (BC) subtype with limited treatment options due to a lack of estrogen receptor alpha (ERα), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2/neu) expression....

Descripción completa

Detalles Bibliográficos
Autores principales: Alexandrova, Elena, Lamberti, Jessica, Saggese, Pasquale, Pecoraro, Giovanni, Memoli, Domenico, Mirici Cappa, Valeria, Ravo, Maria, Iorio, Roberta, Tarallo, Roberta, Rizzo, Francesca, Collina, Francesca, Cantile, Monica, Di Bonito, Maurizio, Botti, Gerardo, Nassa, Giovanni, Weisz, Alessandro, Giurato, Giorgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226848/
https://www.ncbi.nlm.nih.gov/pubmed/32260128
http://dx.doi.org/10.3390/cells9040874
_version_ 1783534376249720832
author Alexandrova, Elena
Lamberti, Jessica
Saggese, Pasquale
Pecoraro, Giovanni
Memoli, Domenico
Mirici Cappa, Valeria
Ravo, Maria
Iorio, Roberta
Tarallo, Roberta
Rizzo, Francesca
Collina, Francesca
Cantile, Monica
Di Bonito, Maurizio
Botti, Gerardo
Nassa, Giovanni
Weisz, Alessandro
Giurato, Giorgio
author_facet Alexandrova, Elena
Lamberti, Jessica
Saggese, Pasquale
Pecoraro, Giovanni
Memoli, Domenico
Mirici Cappa, Valeria
Ravo, Maria
Iorio, Roberta
Tarallo, Roberta
Rizzo, Francesca
Collina, Francesca
Cantile, Monica
Di Bonito, Maurizio
Botti, Gerardo
Nassa, Giovanni
Weisz, Alessandro
Giurato, Giorgio
author_sort Alexandrova, Elena
collection PubMed
description Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, representing the most aggressive breast cancer (BC) subtype with limited treatment options due to a lack of estrogen receptor alpha (ERα), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2/neu) expression. Estrogen receptor beta (ERβ) is present in a fraction of TNBC patients, where its expression correlates with improved patient outcomes, supported by the fact that it exerts oncosuppressive effects in TNBC cell models in vitro. ERβ is involved in microRNA-mediated regulation of gene expression in hormone-responsive BC cells and could mediate its actions through small noncoding RNAs (sncRNAs) in TNBCs also. To verify this possibility, smallRNA sequencing was performed on three ERβ-expressing cell lines from different TNBC molecular subtypes. Several sncRNAs resulted modulated by ERβ, with a subset being regulated in a tumor subtype-independent manner. Interestingly, sncRNA profiling of 12 ERβ+and 32 ERβ− primary TNBC biopsies identified 7 microRNAs, 1 PIWI-interacting RNA (piRNA), and 1 transfer RNA (tRNA) differentially expressed in ERβ+ compared to ERβ− tumors and cell lines. Among them, miR-181a-5p was found to be overexpressed in ERβ+ tumors and predicted target key components of the cholesterol biosynthesis pathway previously found to be inhibited by ERβ in TNBC cells.
format Online
Article
Text
id pubmed-7226848
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72268482020-05-18 Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer Alexandrova, Elena Lamberti, Jessica Saggese, Pasquale Pecoraro, Giovanni Memoli, Domenico Mirici Cappa, Valeria Ravo, Maria Iorio, Roberta Tarallo, Roberta Rizzo, Francesca Collina, Francesca Cantile, Monica Di Bonito, Maurizio Botti, Gerardo Nassa, Giovanni Weisz, Alessandro Giurato, Giorgio Cells Article Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, representing the most aggressive breast cancer (BC) subtype with limited treatment options due to a lack of estrogen receptor alpha (ERα), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2/neu) expression. Estrogen receptor beta (ERβ) is present in a fraction of TNBC patients, where its expression correlates with improved patient outcomes, supported by the fact that it exerts oncosuppressive effects in TNBC cell models in vitro. ERβ is involved in microRNA-mediated regulation of gene expression in hormone-responsive BC cells and could mediate its actions through small noncoding RNAs (sncRNAs) in TNBCs also. To verify this possibility, smallRNA sequencing was performed on three ERβ-expressing cell lines from different TNBC molecular subtypes. Several sncRNAs resulted modulated by ERβ, with a subset being regulated in a tumor subtype-independent manner. Interestingly, sncRNA profiling of 12 ERβ+and 32 ERβ− primary TNBC biopsies identified 7 microRNAs, 1 PIWI-interacting RNA (piRNA), and 1 transfer RNA (tRNA) differentially expressed in ERβ+ compared to ERβ− tumors and cell lines. Among them, miR-181a-5p was found to be overexpressed in ERβ+ tumors and predicted target key components of the cholesterol biosynthesis pathway previously found to be inhibited by ERβ in TNBC cells. MDPI 2020-04-03 /pmc/articles/PMC7226848/ /pubmed/32260128 http://dx.doi.org/10.3390/cells9040874 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
Alexandrova, Elena
Lamberti, Jessica
Saggese, Pasquale
Pecoraro, Giovanni
Memoli, Domenico
Mirici Cappa, Valeria
Ravo, Maria
Iorio, Roberta
Tarallo, Roberta
Rizzo, Francesca
Collina, Francesca
Cantile, Monica
Di Bonito, Maurizio
Botti, Gerardo
Nassa, Giovanni
Weisz, Alessandro
Giurato, Giorgio
Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer
title Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer
title_full Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer
title_fullStr Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer
title_full_unstemmed Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer
title_short Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer
title_sort small non-coding rna profiling identifies mir-181a-5p as a mediator of estrogen receptor beta-induced inhibition of cholesterol biosynthesis in triple-negative breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226848/
https://www.ncbi.nlm.nih.gov/pubmed/32260128
http://dx.doi.org/10.3390/cells9040874
work_keys_str_mv AT alexandrovaelena smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT lambertijessica smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT saggesepasquale smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT pecorarogiovanni smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT memolidomenico smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT miricicappavaleria smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT ravomaria smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT iorioroberta smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT taralloroberta smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT rizzofrancesca smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT collinafrancesca smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT cantilemonica smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT dibonitomaurizio smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT bottigerardo smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT nassagiovanni smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT weiszalessandro smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer
AT giuratogiorgio smallnoncodingrnaprofilingidentifiesmir181a5pasamediatorofestrogenreceptorbetainducedinhibitionofcholesterolbiosynthesisintriplenegativebreastcancer