TY - JOUR
T1 - UBE2C expression is elevated in hepatoblastoma and correlates with inferior patient survival
AU - Nousiainen, Ruth
AU - Eloranta, Katja
AU - Isoaho, Noora
AU - Cairo, Stefano
AU - Wilson, David B.
AU - Heikinheimo, Markku
AU - Pihlajoki, Marjut
N1 - Publisher Copyright:
Copyright © 2023 Nousiainen, Eloranta, Isoaho, Cairo, Wilson, Heikinheimo and Pihlajoki.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - UBE2C
KW - hepatoblastoma
KW - liver tumor
KW - pediatric cancer
KW - ubiquitin
UR - http://www.scopus.com/inward/record.url?scp=85163619619&partnerID=8YFLogxK
U2 - 10.3389/fgene.2023.1170940
DO - 10.3389/fgene.2023.1170940
M3 - Article
C2 - 37377594
AN - SCOPUS:85163619619
SN - 1664-8021
VL - 14
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 1170940
ER -