HMMR inhibition by 4-methylumbelliferone is effective in preclinical hepatocellular carcinoma models

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dc.contributor.authorGe Sang Wang Dui2
dc.contributor.authorSuo Lang Bai Ma
dc.contributor.authorCi Yang
dc.contributor.authorWen Xu
dc.contributor.authorJianguo Xu
dc.contributor.authorYing Zhu
dc.contributor.departmentBiología Celular e Histología
dc.date.accessioned2025-12-22T09:05:33Z
dc.date.available2025-12-22T09:05:33Z
dc.date.issued2026
dc.description.abstractThe poor prognosis of hepatocellular carcinoma (HCC), especially in advanced stages, underscores the need for new therapeutic strategies. In this study, we show that hyaluronan-mediated motility receptor (HMMR) is highly expressed in HCC tumors compared with normal liver tissues. Knockdown of HMMR using siRNA significantly reduced cell proliferation and migration in both parental and doxorubicin-resistant HCC cell lines without inducing apoptosis. Similarly, treatment with 4-Methyl-umbelliferone (4-MU), a pharmacological HMMR inhibitor, led to dose-dependent decreases in proliferation and migration in vitro. In vivo, 4-MU treatment significantly inhibited tumor growth in a HepG2 xenograft model, resulting in a 44% reduction in tumor volume by day 20 and an 80% decrease in HMMR expression in tumor tissues. These results demonstrate that HMMR promotes growth and migration in HCC, and targeting HMMR effectively inhibits both parental and drug-resistant HCC cells. Additionally, our findings suggest that 4-MU, an approved drug for biliary tract disorders, holds promise as a repurposed therapeutic candidate for HCC treatment.
dc.formatapplication/pdf
dc.format.extent7
dc.identifier.doihttps://doi.org/10.14670/HH-18-937
dc.identifier.eissn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/181849
dc.languageeng
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologia
dc.relationSin financiacion externa a la Universidad
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHCC
dc.subjectChemoresistance
dc.subject4-MU
dc.subjectHMMR
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleHMMR inhibition by 4-methylumbelliferone is effective in preclinical hepatocellular carcinoma models
dc.typeinfo:eu-repo/semantics/article
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Histology and histopathology, Vol.41, Nº1, (2026)