Journal of Liver

Molecular links between inflammation, NAFLD and HCC in the context of Ncoa5 deficiency

2^nd International Conference on Hepatology

May 09-11, 2016 Chicago, USA

Hua Xiao

Michigan State University, USA

Posters & Accepted Abstracts: J Liver

Abstract:

Hepatocellular carcinoma (HCC) is the fifth most common and the third most lethal cancer worldwide with increasing incidence in developed countries including the United States. It is estimated that 15-50% of HCC patients develop HCC in the absence of eminent etiological factors such as hepatitis viral infection and alcohol abuse. Emerging evidence has indicated that metabolic disorders such as non alcoholic fatty liver disease (NAFLD) and type-2 diabetes (T2D) are linked to HCC development, which may account for the increasing incidence of HCC in developed countries. Our laboratory previously reported that male mice bearing heterozygous deletion of Ncoa5 gene developed glucose intolerance, NAFLD and HCC. This mouse model of HCC offers a genetically defined system for exploring the mechanisms underlying HCC in the context of glucose dysregulation, inflammation and NAFLD. We compared hepatic gene expression between wild type and Ncoa5+/- male mice at a premalignant stage by RNA-seq transcriptome profiling and found differentially expressed genes involved in the pathogenesis of Inflammation, NAFLD and HCC. The HCC development was paralleled with increased expression of several key pro inflammatory cytokines and enzymes involved in inflammation and fatty acid synthesis in livers. We further show that heterozygous deletion of IL-6 rescues phenotypes of hepatic steatosis, aberrant sperm morphology and motility occurring in male mice with Ncoa5 heterozygous deletion, suggesting the importance of Interleukin 6 (IL-6) in the development of these pathogenic conditions. Together, our results provide novel insight into molecular mechanisms underlying HCC development.

Biography :

Email: xiaoh@msu.edu