MiR-301a-3p Suppresses Estrogen Signaling by Directly Inhibiting ESR1 in ERα Positive Breast Cancer

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F18%3A10379629" target="_blank" >RIV/00216208:11140/18:10379629 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/18:10379629

Result on the web

<a href="http://dx.doi.org/10.1159/000489687" target="_blank" >http://dx.doi.org/10.1159/000489687</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1159/000489687" target="_blank" >10.1159/000489687</a>

Result language

angličtina

Original language name

MiR-301a-3p Suppresses Estrogen Signaling by Directly Inhibiting ESR1 in ERα Positive Breast Cancer

Original language description

BACKGROUND/AIMS: MiRNA-301a-3p is an oncogenic miRNA whose expression is associated with tumor development, metastases and overall poor prognosis. Estrogen receptor α (ERα) is one of the estrogen hormone-activated transcription factors, which regulates a large number of genes and is involved in the mammary gland development. Expression of ERα is considered to be a good indicator for endocrine therapy and breast cancer survival. Loss of ERα in breast cancer patients indicates invasiveness and poor prognosis. In this study, we focus on the regulation of ERα by miR-301a and its role in transition from estrogen-dependent to estrogen-independent breast cancer. METHODS: Expression of miR-301a-3p was measured by qRT-PCR in tumor tissue samples from 111 patients with primary breast carcinoma and in mammospheres representing in vitro model of cancer stem-like cells. Dual reporter luciferase assay and complementary experiments were performed to validate ESR1 as a direct target of miR-301a-3p. The effect of miR-301a-3p on estrogen signaling was evaluated on the level of gene and protein expression and growth response to estrogens. Finally, the effect of miR-301a-3p expression on tumor growth was studied in nude mice. RESULTS: We identified ESR1 as a direct target of miR-301a-3p. Ectopic miR-301a-3p causes a decrease in ESR1 mRNA and protein level and modulates the expression of ERα target genes in ERα positive breast cancer cells. Consistently, miR-301a-3p causes a decrease in sensitivity of MCF7 cells to 17β-estradiol and inhibits the growth of estrogen dependent tumor in nude mice. Yet, the mice tumors have significantly increased expression of genes related to cancer stem-like cells and epithelial to mesenchymal transition suggesting enrichment of the population of cells with more invasive properties, in line with our observation that miR-301a-3p expression is highly increased in mammospheres which show a decrease in estrogenic signaling. Importantly, miR-301a-3P level is also increased in primary breast cancer samples exhibiting an ER/PR negative phenotype. CONCLUSION: Our results confirm ESR1 as a direct target of miR-301a-3p and suggest that miR-301a-3p likely contributes to development of estrogen independence, which leads to a more invasive phenotype of breast cancer.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/LO1503" target="_blank" >LO1503: BIOMEDIC</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cellular Physiology and Biochemistry

ISSN

1015-8987

e-ISSN

—

Volume of the periodical

46

Issue of the periodical within the volume

6

Country of publishing house

CH - SWITZERLAND

Number of pages

15

Pages from-to

2601-2615

UT code for WoS article

000433251900035

EID of the result in the Scopus database

2-s2.0-85047163482