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Fibroblast growth factor (<jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>) signals play important roles in mesothelioma cell growth. Several <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content> receptors (<jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content>s) are predicted targets of the miR\u201015\/16 family, which is downregulated in <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content>. The aim of this study was to explore the link between the miR\u201015\/16 family and the <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content> axis in <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content>. Expression analyses via <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> showed downregulation of the <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content> axis after transfection with miR\u201015\/16 mimics. Direct interaction was confirmed by luciferase reporter assays. Restoration of miR\u201015\/16 led to dose\u2010dependent growth inhibition in <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> cell lines, which significantly correlated with their sensitivity to <jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content> inhibition. Treatment with recombinant <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>2 prevented growth inhibition and further reduced the levels of <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\/R\u2010targeting micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s, indicating a vicious cycle between miR\u201015\/16 down\u2010 and <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content> signaling upregulation. Combined inhibition of two independent miR\u201015\/16 targets, the <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content> axis and Bcl\u20102, resulted in additive or synergistic activity. Our data indicate that post\u2010transcriptional repression of <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\u2010mediated signals contributes to the tumor suppressor function of the micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u201015\/16 family. Inhibiting hyperactivated <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content> signals and Bcl\u20102 might serve as a novel therapeutic combination strategy in <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content>.<\/jats:p>","DOI":"10.1002\/1878-0261.12150","type":"journal-article","created":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T02:48:45Z","timestamp":1509590925000},"page":"58-73","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A link between the fibroblast growth factor axis and the miR\u201016 family reveals potential new treatment combinations in mesothelioma"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8742-1737","authenticated-orcid":false,"given":"Karin","family":"Schelch","sequence":"first","affiliation":[{"name":"Asbestos Diseases Research Institute Sydney Australia"},{"name":"Department of Medicine I Institute of 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