17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERa-positive breast cancer

被引：23

作者：

Drula, Rares ^{[3
,4
]}

Pardini, Barbara ^{[5
,6
]}

Fu, Xiao ^{[7
,8
]}

De los Santos, Mireia Cruz ^{[7
,9
]}

Jurj, Ancuta ^{[3
,4
]}

Pang, Lan ^{[3
]}

El-Daly, Sherien M. ^{[7
,10
]}

Fabris, Linda ^{[3
]}

Knutsen, Erik ^{[7
,11
,12
]}

Dragomir, Mihnea P. ^{[7
,13
,14
,15
,16
,17
,18
]}

Bayraktar, Recep ^{[3
]}

Li, Yongfeng ^{[7
,19
]}

Chen, Meng ^{[3
]}

Del Vecchio, Filippo ^{[20
]}

Berland, Lea ^{[7
,21
]}

Dae, Jessica ^{[7
,22
]}

Fan, Daniel ^{[3
,22
]}

Shimizu, Masayoshi ^{[3
]}

Tran, Anh M. ^{[7
,23
]}

Barzi, Mercedes ^{[24
]}

Pioppini, Carlotta ^{[7
,25
]}

Gutierrez, Angelica M. ^{[26
]}

Ivan, Cristina ^{[1
,7
,27
]}

Meas, Salyna ^{[28
]}

Hall, Carolyn S. ^{[2
,28
]}

Alahari, Suresh K. ^{[29
]}

Berindan-Neagoe, Ioana ^{[4
]}

Fabbri, Muller ^{[20
,30
]}

Lucci, Anthony ^{[28
]}

Arun, Banu ^{[26
]}

Anfossi, Simone ^{[3
]}

Calin, George A. ^{[3
,27
]}

机构：

[1] Caris Life Sci, 750 W John Carpenter Fwy,Suite 800, Irving, TX 75039 USA

[2] Exact Sci, 5505 Endeavor Lane, Madison, WI 53719 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[4] Iuliu Hatieganu Univ Med & Pharm, Res Ctr Funct Genom Biomed & Translat Med, Cluj Napoca 400337, Romania

[5] FPO IRCCS Candiolo, Italian Inst Genom Med, I-10060 Candiolo, Italy

[6] FPO IRCCS, Candiolo Canc Inst, I-10060 Candiolo, Italy

[7] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

[8] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Med Oncol, Xian 710061, Shaanxi, Peoples R China

[9] Karolinska Univ Hosp, Karolinska Inst, Dept Oncol Pathol, S-17164 Solna, Sweden

[10] Natl Res Ctr, Med Res & Clin Studies Inst, Med Biochem Dept, Cairo 12622, Egypt

[11] UiT Artic Univ Norway, Fac Hlth Sci, Dept Med Biol, N-9037 Tromso, Norway

[12] Univ Hosp North Norway, Ctr Clin Res & Educ, N-9037 Tromso, Norway

[13] Charite Univ Med Berlin, Inst Pathol, D-10178 Berlin, Germany

[14] Free Univ Berlin, D-10178 Berlin, Germany

[15] Humboldt Univ, D-10178 Berlin, Germany

[16] German Canc Res Ctr, Partner Site Berlin, D-69120 Heidelberg, Germany

[17] German Canc Consortium DKTK, D-69120 Heidelberg, Germany

[18] Berlin Inst Hlth, D-10178 Berlin, Germany

[19] Zhejiang Canc Hosp, Dept Breast Surg, Hangzhou 310022, Zhejiang, Peoples R China

[20] Univ Hawaii Canc Ctr, Canc Biol Program, Honolulu, HI 96813 USA

[21] Dana Farber Canc Inst, Dept Res Imaging, Boston, MA 02215 USA

[22] Univ Texas Austin, Coll Nat Sci, Austin, TX 78712 USA

[23] Mt Holyoke Coll, Dept Chem, South Hadley, MA 01075 USA

[24] Duke Univ, Dept Pediat, Durham, NC 27708 USA

[25] Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, D-10117 Berlin, Germany

[26] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Div Canc Med, Houston, TX 77030 USA

[27] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Houston, TX 77030 USA

[28] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Breast Surg Oncol, Houston, TX 77030 USA

[29] Louisiana State Univ, Stanley S Scott Canc Ctr, Dept Biochem & Mol Biol, Sch Med, New Orleans, LA 70112 USA

[30] Childrens Natl Hosp, Ctr Canc & Immunol Res, Washington, DC 20010 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2023年 / 120卷 / 23期

关键词：

estrogen receptor; extracellular vesicles; exosomes; breast cancer; microRNAs; COUPLED ESTROGEN RECEPTOR-1; HNRNP A1; MACROPHAGE POLARIZATION; RESPONSE ELEMENTS; SPLICING FACTORS; NONCODING RNAS; MESSENGER-RNAS; MICRORNAS; CELLS; GENES;

D O I：

10.1073/pnas.2122053120

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 17 beta-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17 beta-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 17 beta-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.

引用

页数：11

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