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Article
Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and miR-122-mediated HIF-1alpha activation
Open Access Articles
  • Aditya Ambade, University of Massachusetts Medical School
  • Abhishek Satishchandran, University of Massachusetts Medical School
  • Gyongyi Szabo, University of Massachusetts Medical School
UMMS Affiliation
Department of Medicine, Division of Gastroenterology; UMass Metabolic Network
Publication Date
2-18-2016
Document Type
Article
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-1alpha 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.

Keywords
  • Cancer models
Rights and Permissions
Copyright © 2016, The Author(s).
DOI of Published Version
10.1038/srep21340
Source
Sci Rep. 2016 Feb 18;6:21340. doi: 10.1038/srep21340. Link to article on publisher's site
Related Resources
Link to Article in PubMed
PubMed ID
26888602
Creative Commons License
Creative Commons Attribution 4.0
Citation Information
Aditya Ambade, Abhishek Satishchandran and Gyongyi Szabo. "Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and miR-122-mediated HIF-1alpha activation" Vol. 6 (2016) ISSN: 2045-2322 (Linking)
Available at: http://works.bepress.com/gyongyi_szabo/199/