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The pathogenic basis of miR\u201017\u201092 cluster remains unclear although the oncogenic microRNA (miRNA) miR\u201017\u201092 cluster is highly expressed in patients with MCL. We revealed that miR\u201017\u201092 cluster overexpression is partly dependent on SOX11 expression and chromatin acetylation of <jats:italic>MIR17HG<\/jats:italic> enhancer regions. Moreover, miR\u201017\u201092 cluster regulates not only cell proliferation but BCR signaling activation in MCL cell lines. To comprehensively identify miR\u201017\u201092 cluster target genes, we performed pulldown\u2010seq, where target RNA of miRNA was captured using the biotinylated miRNA mimics and magnetic bead\u2010coated streptavidin, and quantified using next\u2010generation sequencing. The pulldown\u2010seq identified novel miRNA target genes, including tumor suppressors such as <jats:italic>BTG2<\/jats:italic> (miR\u201019b), <jats:italic>CDKN2A<\/jats:italic> (miR\u201017), <jats:italic>SYNE1<\/jats:italic> (miR\u201020a), <jats:italic>TET2<\/jats:italic> (miR\u201018, miR\u201019b, and miR\u201092a), <jats:italic>TNFRSF10A<\/jats:italic> (miR\u201092a), and <jats:italic>TRAF3<\/jats:italic> (miR\u201017). Notably, the gene expression profile data of patients with MCL revealed that BTG2 expression was negatively associated with that of BCR signature genes, and low BTG2 expression was associated with poor overall survival. Moreover, BTG2 silencing in MCL cell lines significantly induced BCR signaling overactivation and cell proliferation. Our results suggest an oncogenic role of miR\u201017\u201092 cluster\u2010activating BCR signaling throughout BTG2 deregulation in MCL. Furthermore, this may contribute to the prediction of the therapeutic efficacy and improved outcomes of MCL.<\/jats:p>","DOI":"10.1111\/cas.16027","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T08:30:17Z","timestamp":1701765017000},"page":"452-464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["miR\u201017\u201092 cluster\u2010BTG2 axis regulates B\u2010cell receptor signaling in mantle cell lymphoma"],"prefix":"10.1111","volume":"115","author":[{"given":"Yuka","family":"Kawaji\u2010Kanayama","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6803-5491","authenticated-orcid":false,"given":"Taku","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Department of 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