Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and MIR-122-mediated HIF-1α activation

Aditya Ambade, Abhishek Satishchandran, G. Szabó

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Alcohol-related hepatocellular carcinoma (HCC) develops with advanced alcoholic liver disease and liver fibrosis. Using adult mice, we evaluate the effect of alcoholic steatohepatitis on early hepatobiliary carcinoma after initiation by diethyl-nitrosamine (DEN). Here we show that alcohol-fed DEN-injected mice have higher ALT and liver-to-body weight ratio compared to pair-fed DEN-injected mice. Alcohol feeding results in steatohepatitis indicated by increased pro-inflammatory cytokines and fibrotic genes. MRI and liver histology of alcohol+DEN mice shows hepatobiliary cysts, early hepatic neoplasia and increase in serum alpha-fetoprotein. Proliferation makers (BrdU, cyclin D1, p53) and cancer stem cell markers (CD133 and nanog) are significantly up-regulated in livers of alcohol-fed DEN-injected mice compared to controls. In livers with tumors, loss of miR-122 expression with a significant up-regulation of miR-122 target HIF-1α is seen. We conclude that alcoholic steatohepatitis accelerates hepatobiliary tumors with characteristic molecular features of HCC by up-regulating inflammation, cell proliferation, stemness, and miR-122 loss.

Original languageEnglish
Article number21340
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Feb 18 2016

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Alcoholic Hepatitis
Nitrosamines
Alcohols
Alcoholic Fatty Liver
Liver
Neoplasms
Hepatocellular Carcinoma
Alcoholic Liver Diseases
Neoplastic Stem Cells
Cyclin D1
alpha-Fetoproteins
Fatty Liver
Bromodeoxyuridine
Liver Cirrhosis
Cysts
Histology
Up-Regulation
Body Weight
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • General

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Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and MIR-122-mediated HIF-1α activation. / Ambade, Aditya; Satishchandran, Abhishek; Szabó, G.

In: Scientific Reports, Vol. 6, 21340, 18.02.2016.

Research output: Contribution to journalArticle

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