{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318086/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Non-coding RNA profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318086"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A combinatorial EVs-miRNA signature mediates the anti-tumoral activity of NFAT3- regulated extracellular vesicles in aggressive cancers.","description":"Aggressive cancers such as triple-negative breast cancer (TNBC) and pancreatic cancer remain difficult to treat because their malignant behavior is driven by complex gene networks rather than single oncogenic targets. Our study identifies a NFAT3 transcription factor-dependent miRNAs signature that suppresses tumor aggressiveness through extracellular vesicles (EVs). Functional analyses demonstrated that a specific combination of fifteen miRNAs (miR-Comb 15) is required to inhibit cancer cell proliferation and invasion across TNBC and pancreatic cancer models, whereas individual miRNA are insufficient to reproduce the full anti-tumoral effect. To enable therapeutic translation, we engineered EVs derived from HEK 293T, a non- tumoral and scalable vesicle source. Using an optimized exogenous pH-gradient loading strategy, miR-Comb 15 was efficiently incorporated into EVs without altering their integrity or intrinsic bioactivity. Among multiple delivery platforms tested, miR-Comb 15 loaded HEK 293T EVs consistently exhibited superior anti-tumoral efficacy both in vitro and in vivo. Together, these findings establish a strong mechanistic link between transcriptional regulation and EVs-mediated RNA delivery and demonstrates that rationally designed RNA combinations delivered by EVs represent a promising therapeutic strategy for aggressive cancers.","dates":{"publication":"2026/08/09"},"accession":"GSE318086","cross_references":{"GSM":["GSM9486066","GSM9486067","GSM9486073","GSM9486074","GSM9486071","GSM9486072","GSM9486070","GSM9486068","GSM9486069"],"GPL":["18573"],"GSE":["318086"],"taxon":["Homo sapiens"]}}