{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:47:32Z","timestamp":1792450052715,"version":"4.5.0"},"reference-count":61,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T00:00:00Z","timestamp":1587081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001755","name":"Mesothelioma Applied Research Foundation","doi-asserted-by":"publisher","award":["483418"],"award-info":[{"award-number":["483418"]}],"id":[{"id":"10.13039\/100001755","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Malignant mesothelioma (MM) is an aggressive asbestos\u2010related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)\u2010deficient cancers, in which the accumulation of the substrate 5'\u2010methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the <jats:italic>MTAP<\/jats:italic> gene is frequently codeleted with the adjacent cyclin\u2010dependent kinase inhibitor 2A (<jats:italic>CDKN2A<\/jats:italic>) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable <jats:italic>PRMT5<\/jats:italic> knock\u2010down, by short hairpin RNAs (shRNAs), selectively reduced the growth of <jats:italic>MTAP<\/jats:italic>\u2010deleted MM cells. We also observed that <jats:italic>PRMT5<\/jats:italic> knock\u2010down in <jats:italic>MTAP<\/jats:italic>\u2010deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial\u2010to\u2010mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against <jats:italic>MTAP<\/jats:italic>\u2010deleted MMs.<\/jats:p>","DOI":"10.1111\/jcmm.15213","type":"journal-article","created":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T08:53:32Z","timestamp":1587113612000},"page":"5565-5577","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["PRMT5 silencing selectively affects <i>MTAP<\/i>\u2010deleted mesothelioma: In vitro evidence of a novel promising approach"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-9814","authenticated-orcid":false,"given":"Marcella","family":"Barbarino","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"},{"name":"Sbarro Institute for Cancer Research and Molecular Medicine Center for Biotechnology College of Science and Technology Temple University 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