Abstract 3059: Targeting tumor progression: The impact of SMR peptide and miRNA on exosome-inflammasome-EMT axis in breast cancer

Abstract Background: In breast cancer, the interplay between exosomes, the inflammasome, and epithelial-mesenchymal transition (EMT) significantly influences tumor progression and metastasis. Exosomes carry molecules that affect cellular processes like inflammation and EMT. The inflammasome produces pro-inflammatory cytokines, promoting tumor-associated inflammation and stimulating EMT, which enhances cancer cell invasiveness. Exosomes also deliver miRNAs that modulate gene expression and promote EMT. Objective: This study investigates the role of the secretion modification region (SMR) peptide in regulating interactions between exosomes, the inflammasome, and EMT in breast cancer, focusing on miRNA influence on gene expression. Methods: MDA-MB-231 breast cancer cells were treated with tumor exosomes or exSMRwt. Exosomes were isolated and characterized using nanoparticle tracking analysis. Inflammasome activation was assessed by measuring caspase-1 and pro-inflammatory cytokines (IL-1β, IL-18). miRNA expression was evaluated using the nCounter Human miRNA assay. Results: The SMR peptide suppressed MDA-MB-231 cell activity and inhibited exosome release, crucial for cancer progression. exSMRwt-treated cells showed reduced inflammasome activity and altered miRNA expression, with significant upregulation and downregulation of specific miRNAs. Nine miRNAs were identified as closely related to breast cancer progression, inhibiting cell proliferation, EMT, migration, invasion, and metastasis. Conclusion: The SMR peptide is a promising therapeutic agent in breast cancer, targeting multiple pathways involved in tumor progression. It inhibits inflammasome activation, reduces pro-inflammatory cytokine production, and modulates exosome-mediated signaling. The peptide also influences miRNA regulation, suppressing inflammation and inhibiting tumor growth and metastasis. This study highlights the therapeutic potential of the SMR peptide and provides direction for further miRNA research in breast cancer. Citation Format: Ming Bo Huang, Erica L. Johnson, Lily Yang, Jonathan Stiles, Aykut Uren, Fengxia Yan, Vincent C. Bond. Targeting tumor progression: The impact of SMR peptide and miRNA on exosome-inflammasome-EMT axis in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3059.