Journal Article

DKFZ-2023-01067

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer.

Drula, R. ; Pardini, B. ; Fu, X. ; De Los Santos, M. C. ; Jurj, A. ; Pang, L. ; El-Daly, S. M. ; Fabris, L. ; Knutsen, E. ; Dragomir, M.-P.DKFZ* ; Bayraktar, R. ; Li, Y. ; Chen, M. ; Del Vecchio, F. ; Berland, L. ; Dae, J. ; Fan, D. ; Shimizu, M. ; Tran, A. M. ; Barzi, M. ; Pioppini, C. ; Gutierrez, A. M. ; Ivan, C. ; Meas, S. ; Hall, C. S. ; Alahari, S. K. ; Berindan-Neagoe, I. ; Fabbri, M. ; Lucci, A. ; Arun, B. ; Anfossi, S. ; Calin, G. A.

2023
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.2122053120

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.

Keyword(s): breast cancer ; estrogen receptor ; exosomes ; extracellular vesicles ; microRNAs

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Contributing Institute(s):

1. DKTK BE zentral (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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