{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:40:38Z","timestamp":1792690838920,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To explore the underlying mechanism by which low\u2010frequency KRAS mutations result in extensive EndMT occurrence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exosomes derived from primarily cultured brain arteriovenous malformation (bAVMs) and human umbilical vein endothelial cells (HUVECs) transfected with KRAS<jats:sup>G12D<\/jats:sup>, KRAS<jats:sup>WT<\/jats:sup>, or KRAS<jats:sup>NC<\/jats:sup> lentiviruses were isolated, and their effects on HUVECs were identified by western blotting and immunofluorescence staining. The expression levels of exosomal microRNAs (miRNAs) were evaluated by miRNA microarray, followed by functional experiments on miR\u20103131 and detection of its downstream target, and miR\u20103131 inhibitor in reversing the EndMT process induced by KRAS<jats:sup>G12D<\/jats:sup>\u2010transfected HUVECs and bAVM endothelial cells (ECs) were explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exosomes derived from KRAS<jats:sup>G12D<\/jats:sup> bAVM ECs and KRAS<jats:sup>G12D<\/jats:sup>\u2010transfected HUVECs promoted EndMT in HUVECs. MiR\u20103131 levels were highest in the exosomes of KRAS<jats:sup>G12D<\/jats:sup>\u2010transfected HUVECs, and HUVECs transfected with the miR\u20103131 mimic acquired mesenchymal phenotypes. RNA\u2010seq and dual\u2010luciferase reporter assays revealed that PICK1 is the direct downstream target of miR\u20103131. Exosomal miR\u20103131 was highly expressed in KRAS<jats:sup>G12D<\/jats:sup> bAVM<jats:sup>exos<\/jats:sup> compared with non\u2010KRAS\u2010mutant bAVM<jats:sup>exos<\/jats:sup> or HUVEC<jats:sup>exos<\/jats:sup>. Finally, a miR\u20103131 inhibitor reversed EndMT in HUVECs treated with exosomes or the supernatant of KRAS<jats:sup>G12D<\/jats:sup>\u2010transfected HUVECs and KRAS<jats:sup>G12D<\/jats:sup> bAVM ECs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Exosomal miR\u20103131 promotes EndMT in KRAS\u2010mutant bAVMs, and miR\u20103131 might be a potential biomarker and therapeutic target in KRAS<jats:sup>G12D<\/jats:sup>\u2010mutant bAVMs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14103","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T08:10:54Z","timestamp":1675152654000},"page":"1312-1324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Exosomal miR\u20103131 derived from endothelial cells with KRAS mutation promotes EndMT by targeting PICK1 in brain arteriovenous 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