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@ARTICLE{Drula:276347,
author = {R. Drula and B. Pardini and X. Fu and M. C. De Los Santos
and A. Jurj and L. Pang and S. M. El-Daly and L. Fabris and
E. Knutsen and M.-P. Dragomir$^*$ and R. Bayraktar and Y. Li
and M. Chen and F. Del Vecchio and L. Berland and J. Dae and
D. Fan and M. Shimizu and A. M. Tran and M. Barzi and C.
Pioppini and A. M. Gutierrez and C. Ivan and S. Meas and C.
S. Hall and S. K. Alahari and I. Berindan-Neagoe and M.
Fabbri and A. Lucci and B. Arun and S. Anfossi and G. A.
Calin},
title = {17β-estradiol promotes extracellular vesicle release and
selective mi{RNA} loading in {ER}α-positive breast cancer.},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {120},
number = {23},
issn = {0027-8424},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {DKFZ-2023-01067},
pages = {e2122053120},
year = {2023},
abstract = {The causes and consequences of abnormal biogenesis of
extracellular vesicles (EVs) are not yet well understood in
malignancies, including in breast cancers (BCs). Given the
hormonal signaling dependence of estrogen receptor-positive
(ER+) BC, we hypothesized that 17β-estradiol (estrogen)
might influence EV production and microRNA (miRNA) loading.
We report that physiological doses of 17β-estradiol promote
EV secretion specifically from ER+ BC cells via inhibition
of miR-149-5p, hindering its regulatory activity on SP1, a
transcription factor that regulates the EV biogenesis factor
nSMase2. Additionally, miR-149-5p downregulation promotes
hnRNPA1 expression, responsible for the loading of let-7's
miRNAs into EVs. In multiple patient cohorts, we observed
increased levels of let-7a-5p and let-7d-5p in EVs derived
from the blood of premenopausal ER+ BC patients, and
elevated EV levels in patients with high BMI, both
conditions associated with higher levels of 17β-estradiol.
In brief, we identified a unique estrogen-driven mechanism
by which ER+ BC cells eliminate tumor suppressor miRNAs in
EVs, with effects on modulating tumor-associated macrophages
in the microenvironment.},
keywords = {breast cancer (Other) / estrogen receptor (Other) /
exosomes (Other) / extracellular vesicles (Other) /
microRNAs (Other)},
cin = {BE01},
ddc = {500},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37252969},
doi = {10.1073/pnas.2122053120},
url = {https://inrepo02.dkfz.de/record/276347},
}