Genetic and Epigenetic Mechanisms Deregulate the CRL2pVHL Complex in Hepatocellular Carcinoma

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Autor(es): dc.contributorBritish Columbia Cancer Research Institute-
Autor(es): dc.contributorHospital Sírio-Libanes-
Autor(es): dc.contributorBritish Columbia Children’s Hospital Research Institute-
Autor(es): dc.contributorUniversity of British Columbia-
Autor(es): dc.contributorIWK Health Centre-
Autor(es): dc.contributorDalhousie University-
Autor(es): dc.contributorBeatrice Hunter Cancer Research Institute-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorMinatel, Brenda C.-
Autor(es): dc.creatorCohn, David E.-
Autor(es): dc.creatorPewarchuk, Michelle E.-
Autor(es): dc.creatorBarros-Filho, Mateus C.-
Autor(es): dc.creatorSage, Adam P.-
Autor(es): dc.creatorStewart, Greg L.-
Autor(es): dc.creatorMarshall, Erin A.-
Autor(es): dc.creatorTelkar, Nikita-
Autor(es): dc.creatorMartinez, Victor D.-
Autor(es): dc.creatorReis, Patricia P.-
Autor(es): dc.creatorRobinson, Wendy P.-
Autor(es): dc.creatorLam, Wan L.-
Data de aceite: dc.date.accessioned2025-08-21T22:14:16Z-
Data de disponibilização: dc.date.available2025-08-21T22:14:16Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-05-18-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3389/fgene.2022.910221-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/241122-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/241122-
Descrição: dc.descriptionDysregulation of ubiquitin-proteasome pathway genes through copy number alteration, promoter hypomethylation, and miRNA deregulation is involved in cancer development and progression. Further characterizing alterations in these genes may uncover novel drug targets across a range of diseases in which druggable alterations are uncommon, including hepatocellular carcinoma (HCC). We analyzed 377 HCC and 59 adjacent non-malignant liver tissue samples, focusing on alterations to component genes of the widely studied CRL2pVHL E3 ubiquitin ligase complex. mRNA upregulation of the component genes was common, and was correlated with DNA hypomethylation and copy number increase, but many tumours displayed overexpression that was not explained by either mechanism. Interestingly, we found 66 miRNAs, including 39 previously unannotated miRNAs, that were downregulated in HCC and predicted to target one or more CRL2pVHL components. Several miRNAs, including hsa-miR-101-3p and hsa-miR-139-5p, were negatively correlated with multiple component genes, suggesting that miRNA deregulation may contribute to CRL2pVHL overexpression. Combining miRNA and mRNA expression, DNA copy number, and methylation status into one multidimensional survival analysis, we found a significant association between greater numbers of alterations and poorer overall survival for multiple component genes. While the intricacies of CRL2pVHL complex gene regulation require additional research, it is evident that multiple causes for the deregulation of these genes must be considered in HCC, including non-traditional mechanisms.-
Descrição: dc.descriptionCanadian Institutes of Health Research-
Descrição: dc.descriptionCanadian HIV Trials Network, Canadian Institutes of Health Research-
Descrição: dc.descriptionDepartment of Integrative Oncology British Columbia Cancer Research Institute-
Descrição: dc.descriptionDepartment of Oncology Hospital Sírio-Libanes-
Descrição: dc.descriptionBritish Columbia Children’s Hospital Research Institute-
Descrição: dc.descriptionDepartment of Medical Genetics University of British Columbia-
Descrição: dc.descriptionDepartment of Pathology and Laboratory Medicine IWK Health Centre-
Descrição: dc.descriptionDepartment of Pathology Faculty of Medicine Dalhousie University-
Descrição: dc.descriptionBeatrice Hunter Cancer Research Institute-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics and Experimental Research Unity (UNIPEX) Faculty of Medicine São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics and Experimental Research Unity (UNIPEX) Faculty of Medicine São Paulo State University (UNESP)-
Idioma: dc.languageen-
Relação: dc.relationFrontiers in Genetics-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectDNA copy number-
Palavras-chave: dc.subjectDNA hypomethylation-
Palavras-chave: dc.subjectliver cancer-
Palavras-chave: dc.subjectnovel microRNAs-
Palavras-chave: dc.subjectubiquitin-proteasome-
Título: dc.titleGenetic and Epigenetic Mechanisms Deregulate the CRL2pVHL Complex in Hepatocellular Carcinoma-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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