{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:40:12Z","timestamp":1776775212264,"version":"3.51.2"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI Grants","doi-asserted-by":"publisher","award":["15H04920"],"award-info":[{"award-number":["15H04920"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI Grants","doi-asserted-by":"publisher","award":["24H00642"],"award-info":[{"award-number":["24H00642"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kagoshima Shinsangyo Sousei Investment Limited Partnership"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In pancreatic cancer, cancer stem-like cells (CSCs) contribute to tumor initiation, reduced drug sensitivity, and recurrence. Limited strategies are currently available to target this cell population. Here we used a proteasome-low CSC enrichment system to identify microRNAs that negatively regulate CSC-like properties. From PANC-1 cells expressing a ZsGreen\u2013ODC degron reporter, a proteasome-low population was isolated through sequential fluorescence-activated cell sorting of ZsGreen-positive cells. Molecular and functional analyses confirmed the CSC-like phenotype of this cell population. Integrated in silico analysis was used to select 31 microRNAs predicted to target CSC-related molecules, which were then evaluated by in vitro viability-based screening to identify candidates that selectively suppressed the viability of CSC-like cells, relative to non-CSCs. Moreover, comprehensive miRNA expression profiling revealed that miR-136-5p was downregulated in the CSC-like population and was therefore selected for further analysis. Mechanistically, miR-136-5p directly targets the 3\u2032 untranslated region of DCLK1 and reduces its expression, with a greater reduction in the short isoform. Finally, in a CSC-derived xenograft mouse model, systemic delivery of miR-136-5p using super carbonate apatite nanoparticles significantly suppressed tumor growth. Taken together, these findings suggest that miR-136-5p restoration may provide a therapeutic approach for targeting CSC-driven tumor growth in pancreatic cancer.<\/jats:p>","DOI":"10.3390\/ijms27083686","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:42:45Z","timestamp":1776771765000},"page":"3686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-136-5p Preferentially Suppresses Cancer Stem-like Cells in Pancreatic Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Hiroyuki","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhki","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihori","family":"Kouda","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruijia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingjue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2687-9933","authenticated-orcid":false,"given":"Yoshihiro","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"},{"name":"Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka 558-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Ikeda City Hospital, Ikeda 563-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4552-783X","authenticated-orcid":false,"given":"Daisuke","family":"Okuzaki","sequence":"additional","affiliation":[{"name":"Laboratory for Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naotsugu","family":"Haraguchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Kindai University Nara Hospital, Ikoma 630-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidekazu","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Osaka International Medical and Science Center, Osaka Keisatsu Hospital, Osaka 543-0042, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6959-9574","authenticated-orcid":false,"given":"Hirofumi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"},{"name":"Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Mori","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine, Tokai University, Isehara 259-1193, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3686\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:45:33Z","timestamp":1776771933000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083686"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083686","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]}}}