{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:37:42Z","timestamp":1790753862636,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T00:00:00Z","timestamp":1583107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R01CA204586"],"award-info":[{"award-number":["R01CA204586"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatoblastoma (HB) is the most common pediatric liver malignancy, occurring mainly during the first 4 years of life. Recent studies unraveled the frequent, coordinated activation of Wnt\/\u03b2\u2010catenin and YAP\/Hippo (where YAP is yes\u2010associated protein) pathways in human HB samples. Furthermore, it was found that concomitant overexpression of activated forms of \u03b2\u2010catenin and YAP in the mouse liver triggers HB formation in YAP\/\u03b2\u2010catenin mice. Cyclin\u2010dependent kinases 9 (CDK9) is an elongating kinase, which has been shown to mediate YAP\u2010driven tumorigenesis. The role of CDK9 in HB molecular pathogenesis has not been investigated to date.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CDK9 expression was determined in human HB lesions, HB cell lines, and YAP\/\u03b2\u2010catenin mouse livers. CDK9 was silenced in human HB cell lines and the effects on growth rate and YAP targets were analyzed. Hydrodynamic transfection of YAPS127A and \u2206N90\u2010\u03b2\u2010catenin together with either shCdk9 or control shLuc (where Luc is luciferase) plasmids was employed to assess the requirement of Cdk9 for HB development in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nuclear immunoreactivity for CDK9 protein was more pronounced in human HB samples and YAP\/\u03b2\u2010catenin mouse HB tumor tissues than in corresponding surrounding nontumorous liver tissues. CDK9 protein was also expressed in human HB cell lines. Silencing of CDK9 in human HB cell lines did not lead to consistent effects on HB cell growth or YAP target gene expression. Surprisingly, silencing of Cdk9 led to accelerated liver tumorigenesis in YAP\/\u03b2\u2010catenin mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CDK9 is not a major downstream mediator of YAP oncogenic function in HB development and progression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28221","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T05:35:34Z","timestamp":1583213734000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["CDK9 is dispensable for YAP\u2010driven hepatoblastoma development"],"prefix":"10.1002","volume":"67","author":[{"given":"Xinyan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacy Hubei University of Chinese Medicine  Wuhan China"},{"name":"Department of Bioengineering and Therapeutic Sciences and Liver Center University of California  San Francisco 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