{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:31:44Z","timestamp":1789500704260,"version":"build-2803163510"},"reference-count":64,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda fellowship","doi-asserted-by":"publisher","award":["935566"],"award-info":[{"award-number":["935566"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic cancer poses a major clinical challenge due to its aggressiveness, frequent recurrence, and limited response to current chemotherapeutic approaches. Cancer stem cells (CSCs), particularly pancreatic CSCs (PCSCs), are key drivers of tumor initiation, therapeutic resistance, and disease relapse. MicroRNAs (miRNAs) have emerged as critical regulators of CSC biology and influence self-renewal, pluripotency, and drug resistance through key signaling pathways. To identify PCSC-specific miRNAs, we enriched these cells using the pancreosphere culture method and isolated PCSC+ and PCSC\u2212 populations using FACS based on their expression of CD44, CD24, and CD133 surface markers. MicroRNA microarray analysis revealed 31 differentially expressed miRNAs (DEmiRNAs), of which 10 downregulated miRNAs were involved in pathways regulating pluripotency, including the Wnt\/\u03b2-catenin, TGF-\u03b2, MAPK, and PI3K\/AKT pathways. Then, 2 of these 10 DEmiRNAs, let-7b-5p and miR-24-3p, were selected for experimental validation. Their overexpression in PCSC+ cells inhibited these pathways, downregulated pluripotency factors, and induced differentiation into endocrine and exocrine phenotypes, as confirmed by RT-qPCR, Western blot, and RNA-seq. Functionally, each miRNA reduced sphere formation, increased gemcitabine sensitivity, and suppressed tumorigenicity in vivo, highlighting their potential as therapeutic candidates. Restoring tumor-suppressive miRNA expression may offer a novel strategy to overcome chemoresistance and improve outcomes in pancreatic cancer.<\/jats:p>","DOI":"10.3390\/ijms262211066","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:24:58Z","timestamp":1763375098000},"page":"11066","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["MicroRNAs Let-7b-5p and miR-24-3p as Potential Therapeutic Agents Targeting Pancreatic Cancer Stem Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Maricela","family":"Medrano-Silva","sequence":"first","affiliation":[{"name":"Departamento de Biomedicina Molecular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (CINVESTAV-IPN), Apartado Postal 14-740, Ciudad de M\u00e9xico 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric 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