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The active mutation of G protein subunit alpha q (<jats:italic>GNAQ<\/jats:italic>) or G protein subunit alpha 11 (<jats:italic>GNA11<\/jats:italic>) is a major trigger for UM. Oncolytic adenovirus H101 (H101) is the first oncolytic virus approved for clinical applications in cancer therapy by the China Food and Drug Administration. We investigated whether combining H101 with the downregulation of <jats:italic>GNAQ<\/jats:italic> expression would act synergistically in UM therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three UM cell lines OMM2.3 and 92.1, harboring GNAQ mutation, and OCM1, harboring B\u2010Raf proto\u2010oncogene mutation, were chosen for our research. The cellular toxicity of adenoviral infection and the cell growth rate were measured with a Cell Counting Kit\u20108. Western blot analysis was used to detect GNAQ, p\u2010MEK1\/2, YAP, and p\u2010YAP expression. The apoptosis and cell\u2010cycle distribution of cells were evaluated with annexin\u2010V and propidium iodide staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results revealed that OMM2.3 and 92.1 cells were more sensitive to H101 infection than OCM1 cells. <jats:italic>GNAQ<\/jats:italic> expression was markedly reduced by small interfering RNA, siGNAQ. Combined treatment of siGNAQ and H101 inhibited the proliferation and activated the apoptosis of OMM2.3 and 92.1 cells by blocking the phosphorylation of MEK1\/2 and increasing the phosphorylation of YAP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In summary, a therapy combining H101 and siGNAQ is feasible, with potential utility as a novel targeted molecular therapy for UM, especially those carrying a <jats:italic>GNAQ<\/jats:italic> mutation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.27863","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T15:21:42Z","timestamp":1539616902000},"page":"5766-5776","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The oncolytic virus H101 combined with <i>GNAQ<\/i> siRNA\u2010mediated knockdown reduces uveal melanoma cell 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