{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:58:30Z","timestamp":1791863910555,"version":"4.3.4"},"reference-count":93,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Cancer Society (ACS) Diversity in Cancer Research\u2014Cancer Health Equity Research Institutional Development Grant Program","award":["885016\/DI-CRIDG-21-072-01-DICRIDG"],"award-info":[{"award-number":["885016\/DI-CRIDG-21-072-01-DICRIDG"]}]},{"name":"NIH\/NIMHD","award":["U54 RCMI-MSM CTRHD"],"award-info":[{"award-number":["U54 RCMI-MSM CTRHD"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U54MD007602-32"],"award-info":[{"award-number":["U54MD007602-32"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["2U54MD007602-31A1"],"award-info":[{"award-number":["2U54MD007602-31A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies and characterized by pronounced heterogeneity and widespread dysregulation of microRNAs (miRNAs) that influence epithelial-to-mesenchymal transition (EMT) and metastasis. Tumor-derived extracellular vesicles (tEVs) further contribute to TNBC progression by transporting oncogenic cargo that can enhance pro-inflammatory signaling. The synthetic SMRwt peptide has been suggested to modulate oncogenic pathways; however, its effects on EV miRNA composition and inflammatory transcript profiles in TNBC remain unclear. Here, we investigated whether SMRwt alters tEV-associated miRNAs and cytokine transcript signatures relevant to EMT and inflammasome-linked pathways. Extracellular vesicles were isolated from SMR-treated and untreated MDA-MB-231 cells, followed by nanoparticle tracking analysis and small RNA sequencing. SMRwt treatment enriched 11 tumor-suppressive miRNAs (including Let-7a-5p, Let-7b-5p, miR-24-3p, miR-26b-5p, miR-92a-3p, miR-93-5p, and miR-496) previously associated with the regulation of proliferation, EMT, migration, and metastasis. We also observed modest, non-significant decreases (1.01\u20131.27-fold) in oncogenic miR-1200, miR-374a-5p, and miR-937-3p, which have been implicated in the progression of breast, lung, and bone malignancies. Complementary transcriptomic profiling using the NanoString nCounter Breast Cancer 360 Gene Expression Panel (NanoString Technologies, Inc., Seattle, CA, USA) demonstrated reduced expression of inflammasome-associated cytokines in TNBC cells relative to non-tumorigenic controls, including a log2 fold change of \u22121.15 for IL 1\u03b2 (MDA-MB-231 vs. MCF10A). These transcript-level changes suggest potential modulation. Additionally, SMRwt suppresses ASC-mediated caspase-1 activation and reduces IL-1\u03b2 secretion, thereby inhibiting NLRP3 inflammasome signaling. Therefore, we infer that SMRwt simultaneously restores tumor-suppressive miRNA networks and suppresses inflammasome-driven inflammation, supporting its potential as a dual-target therapeutic strategy for TNBC.<\/jats:p>","DOI":"10.3390\/cells15060550","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:50:36Z","timestamp":1773921036000},"page":"550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SMR Peptide Modulates Tumor-Derived Extracellular Vesicles microRNA and Inflammatory Transcript Signatures in TNBC"],"prefix":"10.3390","volume":"15","author":[{"given":"Ming-Bo","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8108-5119","authenticated-orcid":false,"given":"Fengxia","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Community Health and Preventive Medicine, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9180-7590","authenticated-orcid":false,"given":"Uswa","family":"Jadoon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer Y.","family":"Wu","sequence":"additional","affiliation":[{"name":"School of International and Public Affairs, Columbia University, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dara","family":"Brena","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0829-1482","authenticated-orcid":false,"given":"Jonathan","family":"Stiles","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Yang","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4514-5575","authenticated-orcid":false,"given":"Brian M.","family":"Rivers","sequence":"additional","affiliation":[{"name":"Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3999-3076","authenticated-orcid":false,"given":"Vincent C.","family":"Bond","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nri.2016.58","article-title":"Inflammasomes: Mechanism of assembly, regulation and signalling","volume":"16","author":"Broz","year":"2016","journal-title":"Nat. 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