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This is followed by <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> verifications for selected gene and CRAE pair.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Our analysis revealed specific germline mutations linked to Grade 2 (or higher) chemotherapy\u2010induced thrombocytopenia (CIT) and nausea\/vomiting (CINV). Notably, both CRAEs were associated with mutations in the <jats:italic>DLG5<\/jats:italic> gene. We found that <jats:italic>DLG5<\/jats:italic> mutations related to CIT were associated with increased gene expression, while those associated with CINV were linked to suppressed gene expression, as indicated by the Genotype\u2010Tissue Expression (GTEX) database. In megakaryocytes, overexpression of human DLG5 suppressed the hippo signalling pathway and induced YAP expression. In zebrafish, overexpression of human DLG5 not only reduced platelet production but also inhibited thrombus formation. Subsequent qPCR analysis revealed that <jats:italic>DLG5<\/jats:italic> overexpression affected genes involved in cytoskeleton formation and alpha\u2010granule formation, which could impact the normal generation of proplatelets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>We identified a series of germline mutations associated with susceptibility to CIT and CINV. Of particular interest, we demonstrated that induced and suppressed <jats:italic>DLG5<\/jats:italic> expression is respectively related to CIT and CINV. These findings shed light on the involvement of the hippo signalling pathway and <jats:italic>DLG5<\/jats:italic> in the development of CRAEs, providing valuable insights into potential targets for therapeutic interventions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17391","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T07:40:36Z","timestamp":1731397236000},"page":"1090-1106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual effects of <i>DLG5<\/i> (disks large homolog 5 gene) modulation on chemotherapy\u2010induced thrombocytopenia and nausea\/vomiting via the hippo signalling pathway"],"prefix":"10.1111","volume":"182","author":[{"given":"Mingming","family":"Li","sequence":"first","affiliation":[{"name":"The SATCM Key Laboratory for New Resources &amp; Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Department of Pharmacy Second Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[{"name":"The SATCM Key Laboratory for New Resources &amp; Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Second Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Second Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shouhong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Second Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhipeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Second Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunsheng","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of General Surgery Second Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi","family":"Qiu","sequence":"additional","affiliation":[{"name":"The SATCM Key Laboratory for New Resources &amp; Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wansheng","family":"Chen","sequence":"additional","affiliation":[{"name":"The SATCM Key Laboratory for New Resources &amp; Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Department of Pharmacy Second Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"issue":"2","key":"e_1_2_13_2_1","first-page":"S1","article-title":"The concise guide to PHARMACOLOGY 2023\/24: Introduction and other protein targets","volume":"180","author":"Alexander S. 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