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Exosomal Delivery of miR-155 Inhibitor can Suppress Migration, Invasion, and Angiogenesis Via PTEN and DUSP14 in
Javad Razaviyan1, Majid Sirati-Sabet1, Razie Hadavi2
1Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Introduction:
Triple-Negative Breast Cancer (TNBC) is the most common type of breast cancer (BC). In order to develop effective treatments for TNBC, it is vital to identify potential therapeutic targets. Angiogenesis stimulates tumor growth and metastasis in TNBC, and miR-155 plays a crucial role in this process. The exosome is a nano-sized vesicle that carries many cargoes, including miRNAs. The present study investigated the effect of exosomal delivery of miR-155 antagomir on tumor migration, invasion, and angiogenesis in TNBC.
Materials And Methods:
From MDA-MB-231 cells, exosomes were extracted, characterized, and loaded with miR-155 antagomir using electroporation. The expression of miR-155 and its target genes, including PTEN and DUSP14, was analyzed using RTqPCR. The wound-healing and transwell assays were used to measure cell migration and invasion. Furthermore, angiogenesis was evaluated by tube formation and chorioallantoic membrane (CAM) assays.
Results:
The results indicated that exosomal delivery of miR-155 antagomir to HUVEC cells significantly suppressed miR-155 expression while upregulating PTEN and DUSP14. The tube formation properties of HUVEC cells were also significantly reduced following treatment with exosomes containing miR-155 antagomirs, and these results were confirmed using CAM assay. The migration and invasion of MDA-MB-231 cells were significantly reduced after treatment with miR-155 antagomir-loaded exosomes.
Conclusion:
It was found that miR-155 antagomir delivery using exosomes can inhibit migration, invasion, and angiogenesis via PTEN and DUSP14 in TNBC.
Insights
Exosomes carrying miR-155 antagomirs effectively inhibit triple-negative breast cancer (TNBC) cell migration, invasion, and angiogenesis. This targeted delivery upregulates PTEN and DUSP14, offering a potential therapeutic strategy for TNBC.
Area of Science:
- Oncology
- Molecular Biology
- Nanomedicine
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype requiring novel therapeutic targets.
- MicroRNA-155 (miR-155) is implicated in TNBC growth, metastasis, and angiogenesis.
- Exosomes serve as natural nanocarriers for therapeutic molecules like miRNAs.
Purpose of the Study:
- To investigate the efficacy of exosome-mediated delivery of miR-155 antagomir in inhibiting TNBC progression.
- To evaluate the impact of this delivery on tumor cell migration, invasion, and angiogenesis.
- To explore the role of PTEN and DUSP14 as downstream targets.
Main Methods:
- Exosomes were isolated from MDA-MB-231 cells and loaded with miR-155 antagomir via electroporation.
- miR-155 expression and its targets (PTEN, DUSP14) were quantified using RTqPCR.
- Cell migration and invasion were assessed using wound-healing and transwell assays.
- Angiogenesis was evaluated through in vitro tube formation and in vivo chorioallantoic membrane (CAM) assays.
Main Results:
- Exosomal delivery of miR-155 antagomir significantly reduced miR-155 expression in HUVEC cells, upregulating PTEN and DUSP14.
- Angiogenesis, assessed by tube formation and CAM assays, was significantly inhibited.
- TNBC cell migration and invasion were markedly reduced following treatment with miR-155 antagomir-loaded exosomes.
Conclusions:
- Exosomal delivery of miR-155 antagomir represents a promising strategy to suppress TNBC migration, invasion, and angiogenesis.
- The observed effects are mediated through the upregulation of PTEN and DUSP14.
- This approach holds potential for developing targeted therapies against TNBC.
