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Investigation of Ctnnb1 Gene Mutations and Expression in Hepatocellular Carcinoma and Cirrhosis in Association With Hepatitis B Virus Infection Publisher



Javanmard D1 ; Najafi M2 ; Babaei MR3 ; Karbalaie Niya MH4 ; Esghaei M1 ; Panahi M4 ; Tameshkel FS4, 5 ; Tavakoli A1 ; Jazayeri SM6, 7 ; Ghaffari H1 ; Ataeipirkooh A1 ; Monavari SH1 ; Bokharaeisalim F1, 8
Authors
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Authors Affiliations
  1. 1. Department of Virology, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Biochemistry, School of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Interventional Radiology, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Student Research Committee, Iran University of Medical Sciences, Tehran, IR, Iran
  6. 6. Department of Virology, Tehran University of Medical Science, Tehran, Iran
  7. 7. Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. HIV Laboratory of National Center, Deputy of Health, Iran University of Medical Sciences, Tehran, Iran

Source: Infectious Agents and Cancer Published:2020


Abstract

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in CTNNB1 gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including c-Myc, promoting the neoplastic process. The present study evaluated the mutational profile of the CTNNB1 gene and expression levels of CTNNB1 and c-Myc genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and c-Myc genes was assessed using real-time PCR. Among the HCC cases, 18.1% showed missense point mutation in exon 3 of CTNNB1, more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4%) rather than HBV-related cases (12.7%, P = 0.021). The expression of β-catenin and c-Myc genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of CTNNB1 gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC. © 2020 The Author(s).