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Chemotherapy-induced exosomal circBACH1 promotes breast cancer resistance and stemness via miR-217/G3BP2 signaling pathway.
- Source :
-
Breast cancer research : BCR [Breast Cancer Res] 2023 Jul 17; Vol. 25 (1), pp. 85. Date of Electronic Publication: 2023 Jul 17. - Publication Year :
- 2023
-
Abstract
- Background: Chemoresistance involves metastasis and aggressiveness of breast cancer (BC). Chemotherapy-elicited exosomes have been reported to be associated with drug resistance and pro-metastatic capacity of BC cells. Non-coding RNAs (ncRNAs) are enriched in exosomes, which participated in generation, progression, and resistance of BC. However, the mechanism underlying the chemoresistance and metastasis in BC cells mediated by the BC-derived exosomal ncRNAs remained to be elucidated.<br />Methods: The effects of PTX-induced exosomal circBACH1 on BC cell function were assessed using RNA Binding Protein Immunoprecipitation (RIP), dual luciferase reporter gene, tube formation, CCK-8, and Western Blot assays. The circBACH1 and miR-217 expression levels were detected using quantitative real-time PCR (RT-qPCR) and Immunohistochemistry (IHC) assays in BC tissues and precancerous tissues of BC patients.<br />Results: CircBACH1 expression was increased in paclitaxel-treated BC-derived exosomes (PTX-EXO) and BC tissue. PTX-EXO was shown to promote PTX-resistance and angiogenesis through upregulation circBACH1. Downregulation of circBACH1 improved PTX-sensitiveness by suppressing the cell viability, stemness, migration, and angiogenesis of BC cells. Moreover, we found that miR-217 interacted with circBACH1 and targeted GTPase-activating SH3 domain-binding protein 2 (G3BP2) in BC cells. CircBACH1 combined miR-217 cotransfection suppressed the expression of G3BP2 proteins compared with circBACH1 treatment in MCF-7 cells. In addition, downregulation of G3BP2 suppressed BC cell migration.<br />Conclusions: These results demonstrated that PTX-induced exosomal circBACH1 promoted stemness and migration of BC cells by sponging miR-217 to upregulate the expression of G3BP2, which provided a new therapeutic target for PTX-resistance and progression of BC via circBACH1/miR-217/G3BP2 axis.<br /> (© 2023. The Author(s).)
- Subjects :
- Female
Humans
Adaptor Proteins, Signal Transducing
Cell Line, Tumor
Cell Proliferation
RNA-Binding Proteins
Signal Transduction
Exosomes genetics
Exosomes metabolism
Antineoplastic Agents therapeutic use
Breast Neoplasms drug therapy
Breast Neoplasms genetics
Breast Neoplasms pathology
MicroRNAs genetics
MicroRNAs metabolism
RNA, Circular genetics
RNA, Circular metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1465-542X
- Volume :
- 25
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Breast cancer research : BCR
- Publication Type :
- Academic Journal
- Accession number :
- 37461019
- Full Text :
- https://doi.org/10.1186/s13058-023-01672-x