{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T14:41:02Z","timestamp":1768747262449,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatoblastoma (HB) is one of the most common cancers in children. Recent studies have shown that the occurrence of nuclear accumulation of \u03b2\u2010catenin reaches 90%\u2013100% because of the anomalous activation of the Wnt pathway in HB patients. Furthermore, emerging studies have shown that concomitant activated forms of YAP and \u03b2\u2010catenin trigger the formation and progression of HB. YAP might play a vital role in \u03b2\u2010catenin\u2010mediated HB development. However, the molecular mechanisms by which YAP\/TEAD4 transcription factor regulates <jats:italic>CTNNB1<\/jats:italic> underlying HB pathogenesis are still unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p><jats:italic>YAP<\/jats:italic> and <jats:italic>CTNNB1<\/jats:italic> expression and correlation were analyzed by a combination of network enrichment analysis and gene set enrichment analysis of the public microarray datasets (GSE131329 and GSE81928). The protein levels of YAP and \u03b2\u2010catenin were further validated by Western blotting in paired patients\u2019 samples. The direct interplay between YAP\/TEAD4 and the promoter region of <jats:italic>CTNNB1<\/jats:italic> was proven by the combination of dual\u2010luciferase report assay and chromatin immunoprecipitation assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>YAP\u2010conserved signature and WNT signaling pathway were significantly enriched in HB patients, with upregulated expression of YAP and \u03b2\u2010catenin compared to non\u2010HB patients. Further functional assays demonstrated that YAP\/TEAD4 transcription factor complex could bind to the <jats:italic>CTNNB1<\/jats:italic> promoter region directly to promote \u03b2\u2010catenin expression and cell proliferation. Targeting the YAP\/TEAD4 complex with a specific small\u2010molecule compound markedly suppressed HepaG2 cell proliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>As the upstream transcription factor of <jats:italic>CTNNB1<\/jats:italic>, YAP\/TEAD4 is a promising target for the treatment of HB patients with high levels of YAP and \u03b2\u2010catenin.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29705","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T13:47:07Z","timestamp":1649684827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Upregulated YAP promotes oncogenic <i>CTNNB1<\/i> expression contributing to molecular pathology of hepatoblastoma"],"prefix":"10.1002","volume":"69","author":[{"given":"Songxian","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery The Third Affiliated Hospital of Zhengzhou 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