Downregulation of GSK3β and Upregulation of URG7 in Hepatitis B-Related Hepatocellular Carcinoma

AuthorDavod Javanmarden
AuthorMohammad Hadi Karbalaie Niyaen
AuthorDavod Khalafkhanyen
AuthorMohammad Najafien
AuthorMasood Ziaeeen
AuthorMohammad Reza Babaeien
AuthorSeyed Jalal Kianien
AuthorMaryam Esghaeien
AuthorSeyed Mohammad Jazayerien
AuthorMahshid Panahien
AuthorFahimeh Safarnezhad Tameshkelen
AuthorMaryam Mehrabien
AuthorSeyed Hamidreza Monavarien
AuthorFarah Bokharaei-Salimen
OrcidDavod Javanmard [0000-0003-0754-9998]en
OrcidMohammad Hadi Karbalaie Niya [0000-0002-1364-5743]en
OrcidMasood Ziaee [0000-0003-0218-6833]en
OrcidSeyed Jalal Kiani [0000-0002-5499-8924]en
OrcidMaryam Esghaei [0000-0003-2944-2147]en
OrcidMahshid Panahi [0000-0001-8005-3273]en
OrcidFahimeh Safarnezhad Tameshkel [0000-0001-8953-5447]en
OrcidSeyed Hamidreza Monavari [0000-0003-1517-6036]en
OrcidFarah Bokharaei-Salim [0000-0002-5367-0847]en
Issued Date2020-08-31en
AbstractHepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC). The exact molecular contributors to the development of HBV-related HCC are not yet completely understood. Recent studies demonstrated that the deregulation of the Wnt pathway is highly associated with the development of HCC. Besides, HBV is known to have roles in the deregulation of this pathway. The present study evaluated the molecular aspects of the Wnt pathway in HBV-related HCC in liver tissue samples. Viral characterization was done by identifying the HBx mutations and the assessment of intrahepatic viral load. The expression of Wnt pathway genes was assessed using real-time PCR and methylation-specific PCR. The intrahepatic viral load was significantly higher in tumor samples than in normal tissues (P = 0.0008). Aberrant expression was observed in Wnt-1, Wnt-7a, FZD2, FZD7, β-catenin, URG7, c-Myc, SFRP5, and GSK3β, among which Wnt1, FZD2, SFRP5, Gsk3β, and URG7 were associated with HBV. HBx mutations at positions I88, L116, and I127 + F132 were associated with the decreased expression of GSK3β and overexpression of URG7 and Wnt1. Alterations in the expression level of β-catenin, as well as some mutants of HBx, were correlated with the level of c-Myc. HBV-related HCC seems to be mostly coordinated with epigenetic behaviors of HBx, such a multi-functional peptide with suppressing/trans-activating functions.en
DOIhttps://doi.org/10.5812/hepatmon.100899en
URIhttps://brieflands.com/journals/hepatmon/articles/100899en
KeywordHBVen
KeywordHCCen
KeywordWnt Pathwayen
KeywordHBxen
KeywordMutationen
KeywordGene Expressionen
PublisherBrieflandsen
TitleDownregulation of GSK3β and Upregulation of URG7 in Hepatitis B-Related Hepatocellular Carcinomaen
TypeResearch Articleen

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