UBE2C expression is elevated in hepatoblastoma and correlates with inferior patient survival

Frontiers in Genetics

Genetics

Stefano Cairo¹  Katja Eloranta²  Ruth Nousiainen²  Marjut Pihlajoki²  Markku Heikinheimo³  Noora Isoaho⁴  David B. Wilson⁵ 

[1] Champions Oncology, Hackensack, NJ, United States;Istituto di Ricerca Pediatrica, Padova, Italy;XenTech, Evry, France;Pediatric Research Center, Children’s Hospital, Helsinki University Hospital, Helsinki, Finland;Pediatric Research Center, Children’s Hospital, Helsinki University Hospital, Helsinki, Finland;Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, MO, United States;Center for Child, Adolescent and Maternal Health Research, Tampere, Finland;School of Electrical Engineering and Computer Science, KTH Royal Institute of Technology, Stockholm, Sweden;Washington University School of Medicine, St. Louis, MO, United States;Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, MO, United States;

关键词: hepatoblastoma;    liver tumor;    pediatric cancer;    ubiquitin;    UBE2C;   

DOI  :  10.3389/fgene.2023.1170940

 received in 2023-02-21, accepted in 2023-05-29,  发布年份 2023

来源: Frontiers

【 摘 要 】

Hepatoblastoma (HB) is the most common malignant liver tumor among children. To gain insight into the pathobiology of HB, we performed RNA sequence analysis on 5 patient-derived xenograft lines (HB-243, HB-279, HB-282, HB-284, HB-295) and 1 immortalized cell line (HUH6). Using cultured hepatocytes as a control, we found 2,868 genes that were differentially expressed in all of the HB lines on mRNA level. The most upregulated genes were ODAM, TRIM71, and IGDCC3, and the most downregulated were SAA1, SAA2, and NNMT. Protein-protein interaction analysis identified ubiquitination as a key pathway dysregulated in HB. UBE2C, encoding an E2 ubiquitin ligase often overexpressed in cancer cells, was markedly upregulated in 5 of the 6 HB cell lines. Validation studies confirmed UBE2C immunostaining in 20 of 25 HB tumor specimens versus 1 of 6 normal liver samples. The silencing of UBE2C in two HB cell models resulted in decreased cell viability. RNA sequencing analysis showed alterations in cell cycle regulation after UBE2C knockdown. UBE2C expression in HB correlated with inferior patient survival. We conclude that UBE2C may hold prognostic utility in HB and that the ubiquitin pathway is a potential therapeutic target in this tumor.

【 授权许可】

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Copyright © 2023 Nousiainen, Eloranta, Isoaho, Cairo, Wilson, Heikinheimo and Pihlajoki.