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The stromal loss of miR-4516 promotes the FOSL1-dependent proliferation and malignancy of triple negative breast cancer

Authors
 Ji Eun Kim  ;  Baek Gil Kim  ;  Yeonsue Jang  ;  Suki Kang  ;  Joo Hyun Lee  ;  Nam Hoon Cho 
Citation
 CANCER LETTERS, Vol.469 : 256-265, 2020 
Journal Title
 CANCER LETTERS 
ISSN
 0304-3835 
Issue Date
2020
Keywords
CAF ; Exosome ; FOSL1 ; Triple negative breast cancer ; miR-4516
Abstract
Stroma-derived exosomal microRNA (exomiR) contributes to tumor progression, however, which remains poorly understood. In our study, we analyzed exomiRs from the cancer-associated fibroblast (CAF) and normal fibroblast (NF) isolated from an invasive ductal carcinoma (IDC) patient and found that the level of microRNA (miR)-4516 was approximately 5-fold lower in CAF-derived exosomes than NF-derived ones. In gene annotation analysis, miR-4516 target genes were mainly associated with the regulation of proliferation. miR-4516 overexpression or mimic treatment suppressed the proliferation of breast cancer cells, especially triple negative breast cancer (TNBC) cells. Among miR-4516 targets, FOSL1 was overexpressed in TNBC cells compared to non-TNBC cells and promoted tumor proliferation. The expression of miR-4516 and FOSL1 was reversely correlated in breast cancer patient tissues. Particularly, TNBC patients with high FOSL1 expression showed a significant poorer survival than those with low FOSL1 expression. Our results show that the loss of miR-4516 from CAF-derived exosomes is associated with FOSL1-dependent TNBC progression and suggest that miR-4516 can be used as an anti-cancer drug for TNBC.
Full Text
https://www.sciencedirect.com/science/article/pii/S0304383519305427
DOI
10.1016/j.canlet.2019.10.039
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Suki(강숙희) ORCID logo https://orcid.org/0000-0002-9957-3479
Kim, Baek Gil(김백길) ORCID logo https://orcid.org/0000-0001-6270-1433
Jang, Yeon Sue(장연수) ORCID logo https://orcid.org/0000-0001-5683-0001
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174891
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