AUTHOR=Nousiainen Ruth , Eloranta Katja , Isoaho Noora , Cairo Stefano , Wilson David B. , Heikinheimo Markku , Pihlajoki Marjut 

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

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1170940

DOI=10.3389/fgene.2023.1170940

ISSN=1664-8021

ABSTRACT=<p>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 <italic>ODAM</italic>, <italic>TRIM71</italic>, and <italic>IGDCC3</italic>, and the most downregulated were <italic>SAA1</italic>, <italic>SAA2</italic>, and <italic>NNMT</italic>. Protein-protein interaction analysis identified ubiquitination as a key pathway dysregulated in HB. <italic>UBE2C</italic>, 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 <italic>versus</italic> 1 of 6 normal liver samples. The silencing of <italic>UBE2C</italic> in two HB cell models resulted in decreased cell viability. RNA sequencing analysis showed alterations in cell cycle regulation after <italic>UBE2C</italic> knockdown. <italic>UBE2C</italic> expression in HB correlated with inferior patient survival. We conclude that <italic>UBE2C</italic> may hold prognostic utility in HB and that the ubiquitin pathway is a potential therapeutic target in this tumor.</p>