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We conducted bioinformatics analysis using Cancer Cell Line Encyclopedia (CCLE) datasets to identify new molecular markers in MM. Overexpression of oxytocin receptor (<jats:italic>OXTR<\/jats:italic>), which is a G\u2010protein\u2013coupled receptor for the hormone and neurotransmitter oxytocin, mRNA was distinctively identified in MM cell lines. Therefore, we assessed the role of <jats:italic>OXTR<\/jats:italic> and its clinical relevance in MM. Kaplan\u2010Meier and Cox regression analyses were applied to assess the association between overall survival and <jats:italic>OXTR<\/jats:italic> mRNA expression using The Cancer Genome Atlas (TCGA) datasets. The function of <jats:italic>OXTR<\/jats:italic> and the efficacy of its antagonists were investigated in vitro and in vivo using MM cell lines. Consistent with the findings from CCLE datasets analysis, <jats:italic>OXTR<\/jats:italic> mRNA expression was highly increased in MM tissues compared with other cancer types in the TCGA datasets, and MM cases with high <jats:italic>OXTR<\/jats:italic> expression showed poor overall survival. Moreover, <jats:italic>OXTR<\/jats:italic> knockdown dramatically decreased MM cell proliferation in cells with high <jats:italic>OXTR<\/jats:italic> expression via tumor cell cycle disturbance, whereas oxytocin treatment significantly increased MM cell growth. <jats:italic>OXTR<\/jats:italic> antagonists, which have high selectivity for OXTR, inhibited the growth of MM cell lines with high <jats:italic>OXTR<\/jats:italic> expression, and oral administration of the <jats:italic>OXTR<\/jats:italic> antagonist, cligosiban, significantly suppressed MM tumor progression in a xenograft model. Our findings suggest that <jats:italic>OXTR<\/jats:italic> plays a crucial role in MM cell proliferation and is a promising therapeutic target that may broaden potential therapeutic options and could be a prognostic biomarker of MM.<\/jats:p>","DOI":"10.1111\/cas.15025","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T17:05:32Z","timestamp":1623431132000},"page":"3520-3532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Oxytocin receptor is a promising therapeutic target of malignant mesothelioma"],"prefix":"10.1111","volume":"112","author":[{"given":"Yuta","family":"Kodama","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5517-0598","authenticated-orcid":false,"given":"Ichidai","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuhiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology Aichi Cancer Center Research Institute Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazumi","family":"Hori","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soei","family":"Gen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Morise","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Tsukuba University Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5458-9576","authenticated-orcid":false,"given":"Mitsuo","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pathophysiological Laboratory Sciences Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Sekido","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology Aichi Cancer Center Research Institute Nagoya Japan"},{"name":"Department of Molecular and Cellular Oncology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2337-629X","authenticated-orcid":false,"given":"Naozumi","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30100-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/sonc.2002.30227"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/oemed-2017-104298"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.09.124"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00007014"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.11.136"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.3190"},{"key":"e_1_2_8_9_1","unstructured":"Highlights of prescribing information.www.fda.gov\/medwatch. 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