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Hepatitis B virus X protein represses LKB1 expression to promote tumor progression and poor postoperative outcome in hepatocellular carcinoma.
Wu, Cheng-Chung; Wu, De-Wei; Lin, Ying-Yu; Lin, Po-Lin; Lee, Huei.
  • Wu CC; Department of General Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
  • Wu DW; Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
  • Lin YY; Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
  • Lin PL; Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
  • Lee H; Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan. Electronic address: hl@tmu.edu.tw.
Surgery ; 163(5): 1040-1046, 2018 05.
Article en En | MEDLINE | ID: mdl-29475611
ABSTRACT

BACKGROUND:

Hepatitis B virus X (HBx) protein plays critical roles in hepatitis B virus (HBV)-associated hepatocellular tumorigenesis through different molecular mechanisms, including inactivation of p53, a key transcription factor of liver kinase B1 (LKB1). We hypothesized that p53 inactivation by HBx protein could decrease LKB1 expression, thereby promoting tumor progression and poor outcomes in patients with HBV-associated hepatocellular carcinoma.

METHODS:

Manipulation strategies for HBx protein and/or p53 were used to verify that loss of LKB1 could promote colony formation and invasiveness in HepG2 and Hep3B cells. The expressions of HBx protein and LKB1 in 93 hepatocellular carcinomas (HCC) were also evaluated by immunohistochemistry. Kaplan-Meier and Cox regression models were used to assess the prognostic value of both HBx protein and LKB1 proteins in patients with hepatocellular carcinoma.

RESULTS:

Mechanistically, LKB1 expression was decreased at the transcriptional level after inactivation of p53 by HBx protein. Decreases in LKB1 expression were also associated with HBx protein-mediated colony formation and invasive capabilities. HBx protein, LKB1, and a combination of both proteins had prognostic significance for overall survival and relapse-free survival in our study population.

CONCLUSION:

The results from cell line experiments and evaluation of patient prognosis according to expression of HBx protein and LKB1 in their HCC strongly support the hypothesis that decreases in LKB1 expression by HBx protein-mediated p53 inactivation may play an important role in HBV-associated hepatocellular tumorigenesis.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Transactivadores / Proteína p53 Supresora de Tumor / Proteínas Serina-Treonina Quinasas / Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male / Middle aged País como asunto: Asia Idioma: En Año: 2018 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Transactivadores / Proteína p53 Supresora de Tumor / Proteínas Serina-Treonina Quinasas / Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male / Middle aged País como asunto: Asia Idioma: En Año: 2018 Tipo del documento: Article