Chemotherapy-induced exosomal circBACH1 promotes breast cancer resistance and stemness via miR-217/G3BP2 signaling pathway

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. 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. 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. 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.

Alpha-hederin reprograms multi-miRNAs activity and overcome small extracellular vesicles-mediated paclitaxel resistance in NSCLC

“…The investigation into the mechanism of sEV-mediated PTX resistance is constrained, especially in terms of data related to lung cancer. Previous studies predominantly delved into the mechanistic roles of sEV cargo, including ANXA6, miR-378a-3p, miR-378d, circBACH1, primarily within the context of breast cancer ( Yang et al, 2021b ; Guo et al, 2021 ; Xia et al, 2023 ). Our study has unveiled the transfer of sEVs in the microenvironment of NSCLC between resistant and sensitive cells and has elucidated the mechanism of PTX resistance, thereby substantially enhancing theoretical comprehension in this domain.…”

Extracellular vesicles as tools and targets in therapy for diseases

“… CircBACH1/ miR-217/G3BP2 axis a new regulatory for PTX-resistance and progression of breast cancer. 672 Cisplatin Ovarian cancer cells A2780, IGROV-1 cells Ovarian cancer CREB, ERK, JNK, p38α, p53 inhibits ovarian cancer 673 , 674 Milk exosomes loaded with cisplatin A2780, nu/nu mice Ovarian cancer ARF6, Rac1, CLTC, caveolin Overcomes cisplatin-resistance in ovarian cancer Temozolomide Glioblastoma cells U87-MG cells, GBM cells Glioblastoma Heat shock protein, RAD51, MDM2 Leads to cell adhesion 675 EVs encapsulated miR-153-3p LUAD cells NCI-H1993, SW1271, BALB/c mice, Lung adenocarcinoma BANCR, miR-153-3p, PI3K/AKT Increases cell invasion 676 EVs PDAC cells MIA PaCa-2, PANC-1,Rag2 −/− Ilrg2 −/−, mice Pancreatic ductal adenocarcinoma Rab27a, LRP-4 receptor, YAP Intratumor communication Targeted therapy for PDAC 677 EVs Human Liver Stem Cells MSCs Renal cancer cells SCID mice Renal cell carcinoma miR-Let7b, miR-200b, miR-200c and miR-223, EGFR, ZEB1, ZEB2, MMP1 antitumor effects 678 …”

Drug resistance in breast cancer is based on the mechanism of exocrine non-coding RNA

“…This provides a therapeutic target for breast cancer treatment [ 81 ]. Furthermore, paclitaxel-induced exosome-derived circBACH1 promotes paclitaxel resistance in recipient breast cancer cells by upregulating G3BP2 expression through sponging miR-217, this upregulation increases cell survival and promotes cell stemness [ 82 ]. These findings present a novel therapeutic target for chemoresistance and metastasis in breast cancer (Fig.…”