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INTERNATIONAL CONGRESS OF

CancerGenetics

• Exosomal microRNAs as a therapeutic approach in breast cancer: A review

• Yeganeh Mobaraki,¹ Sajad Dehnavi,^2,*
  1. Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
  2. Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  
  
  
• Introduction: Breast cancer (BC) is the most common type of malignant disease in women and has a high mortality and incidence rate. Although the absence of metastatic spread and surgical removal of the primary tumor usually results in a “cure”, distant metastases recur in 10% to 30% of patients, sometimes after several years or even decades. Thus, BC has severe effects on quality of life and life expectancy. Furthermore, tumor drug resistance poses a significant challenge to effective clinical treatment. Dysregulated expression of small RNA molecules, particularly microRNAs (miRNAs), plays a pivotal role in mediating this resistance. One way to overcome this cancer is to use exosomal miRNAs. Exosomes are nano-sized biological vesicles released by various types of cells. They transport biomolecules including messenger RNAs (mRNAs), miRNAs, circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs). Exosomes also mediate intercellular communication; regulate the extracellular environment, and influence the expression of downstream genes. Therefore, we have reviewed and summarized relevant studies.
• Methods: Multiple databases, including PubMed, Google Scholar, Web of Science, and Scopus, were searched. Relevant articles published since 2020 were selected and reviewed using the terms “exosomal miRNAs” and “breast cancer treatment”.
• Results: In one study, researchers designed engineered exosomes that displayed human epidermal growth factor receptor 2 (HER2)-binding peptides on their surface and delivered miR-34a. These exosomes were then used to treat of programmed death-ligand 1 (PD-L1)-positive and HER2-positive breast cancer cells. In a mouse model, intravenous administration resulted in improved tumor targeting, significant reductions in tumor weight and volume, decreased PD-L1 expression, and increased cell death. These findings suggest that HER2-targeted exosomes loaded with miR-34a exert notable anticancer effects by binding specifically to HER2-positive cells and suppressing of PD-L1. Another study developed nanoparticles co-loaded with miR-34a and docetaxel that were coated with exosomal membranes derived from RAW264.7 cells. This unique coating distinctly enhanced the uptake of the nanoparticles by BC cells and strengthened their anticancer effects. The nanoparticles effectively inhibited the growth of cancer cell through the controlled release of drugs in acidic tumor environments. The combined action of miR-34a and docetaxel improved therapeutic efficacy. Another assay demonstrated that Notch1 negatively regulated miR-34a. Therefore, overexpressing miRNA-34a could increase apoptosis and decrease cell proliferation in breast cancer cells by reducing the activity of Notch1 signaling pathway.
• Conclusion: With over 2.3 million new cases which is reported worldwide in 2022, BC remains the most prevalent cancer among women. To overcome this cancer, several studies have examined the therapeutic potential of miR-34a in BC. In one study, HER2-binding peptide-displaying exosomes that deliver miR-34a were engineered. In a mouse model, these exosomes increased the apoptosis rate by suppressing PD-L1. Another study co-loaded nanoparticles with miR-34a and docetaxel, coating them with RAW264.7 cell exosomal membranes to increase uptake by BC cells and improve their anticancer effects. Although the previous study illustrated that overexpression of miRNA-34a may decrease cell proliferation, there are some limitations that should be considered, such as the synergistic effects of several miRNAs or their interaction with proteins in exosomes. Nevertheless, further studies are needed to develop a safe treatment for BC.
• Keywords: breast cancer, exosome, miRNA, exosomal miRNA