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The role of miRNA in small extracellular vesicles (sEV) in chemotherapy resistance is under investigation. However, the regulation and sorting mechanism of sEV miRNAs remains unclear. In this study, small RNA sequencing was used to explore miRNA expression profiles in sEV of LSCC after cisplatin stimulation; RNA pull\u2010down, mass spectrometry, and EMSA were used to clarify the binding of candidate RNA\u2010binding protein (RBP) and candidate miRNA. Immunostaining and microRNA fluorescence in\u00a0situ hybridization were performed to identify how candidate RBP affects miRNA stability and nuclear\/cytoplasmic distribution. In\u00a0vivo experiments were performed to verify the biological functions and response to cisplatin of candidate RBP. We found that cisplatin stimulation induced increased expression of miR\u2010148a\u20103p and sEV sorting. ANXA11 binds to miR\u2010148a\u20103p in a sequence\u2010specific manner. ANXA11 inhibits tumor cell proliferation and drug resistance by binding to and retaining miR\u2010148a\u20103p. Cisplatin stimulation reduced ANXA11 expression and promoted miR\u2010148a\u20103p efflux through sEV pathways. ANXA11 overexpression reduced in\u00a0vivo tumor proliferation and cisplatin\u2010resistance. Taken together, ANXA11 mediates cisplatin resistance through sEV miRNA resorting. Mechanically, ANXA11 binds to miR\u2010148a\u20103p in a sequence\u2010specific manner to regulate its resorting and thus influences tumor proliferation and chemoresistance.<\/jats:p>","DOI":"10.1096\/fj.202400841r","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T11:25:06Z","timestamp":1726053906000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Non\u2010canonical\n                    <scp>RNA<\/scp>\n                    \u2010binding protein\n                    <scp>ANXA11<\/scp>\n                    regulates\n                    <scp>microRNA<\/scp>\n                    resorting into small extracellular vesicles to mediate cisplatin resistance"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5110-4657","authenticated-orcid":false,"given":"Yifan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5455-9454","authenticated-orcid":false,"given":"Qiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3647-000X","authenticated-orcid":false,"given":"Yujie","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-5402","authenticated-orcid":false,"given":"Henglei","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0712-8715","authenticated-orcid":false,"given":"Chunping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8588-2959","authenticated-orcid":false,"given":"Liang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai 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