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However, the expression pattern and biological role of LARP1 in hepatoblastoma (HB) remain unclear so far.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>LARP1 expression level in HB and adjacent normal liver tissues was analysed by qRT\u2010PCR, Western blotting and immunohistochemistry assays. The prognostic significance of LARP1 was evaluated by Kaplan\u2013Meier method and multivariate Cox regression analysis. In vitro and in vivo functional assays were implemented to clarify the biological effects of LARP1 on HB cells. Mechanistically, the regulatory roles of <jats:italic>O<\/jats:italic>\u2010GlcNAcylation and circCLNS1A in LARP1 expression were investigated by co\u2010immunoprecipitation (co\u2010IP), immunofluorescence, RNA immunoprecipitation (RIP), RNA pull\u2010down and protein stability assays. Moreover, RNA\u2010sequencing, co\u2010IP, RIP, mRNA stability and poly(A)\u2010tail length assays were performed to investigate the association between LARP1 and DKK4. The expression and diagnostic significance of plasma DKK4 protein in multi\u2010centre cohorts were evaluated by ELISA and ROC curves.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>LARP1 mRNA and protein levels were remarkably elevated in HB tissues and associated with worse prognosis of HB patients. LARP1 knockdown abolished cell proliferation, triggered cell apoptosis in vitro as well as prohibited tumour growth in vivo, whereas LARP1 overexpression incited HB progression. Mechanistically, <jats:italic>O<\/jats:italic>\u2010GlcNAcylation of LARP1 Ser672 by <jats:italic>O<\/jats:italic>\u2010GlcNAc transferase strengthened its binding to circCLNS1A and then protected LARP1 from TRIM\u201025\u2010mediated ubiquitination and proteolysis. LARP1 upregulation subsequently led to DKK4 mRNA stabilisation by competitively interacting with PABPC1 to prevent DKK4 mRNA from B\u2010cell translocation gene 2\u2010dependent deadenylation and degradation, thus facilitating \u03b2\u2010catenin protein expression and nuclear import.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study indicates that upregulated protein level of <jats:italic>O<\/jats:italic>\u2010GlcNAcylated LARP1 mediated by circCLNS1A promotes the tumorigenesis and progression of HB through LARP1\/DKK4\/\u03b2\u2010catenin axis. Hence, LARP1 and DKK4 are promising therapeutical target and diagnostic\/prognostic plasma biomarker for HB.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1239","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T06:58:18Z","timestamp":1681801098000},"source":"Crossref","is-referenced-by-count":17,"title":["<i>O<\/i>\u2010GlcNAcylated LARP1 positively regulated by circCLNS1A facilitates hepatoblastoma progression through DKK4\/\u03b2\u2010catenin signalling"],"prefix":"10.1002","volume":"13","author":[{"given":"Zhongqi","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Shanghai Tenth People's Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangtu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Shanghai Tenth People's Hospital, School of Medicine Tongji University  Shanghai 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