Identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling
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Ali Zamani1,3,*, Huahao Fan1,2,* and Guangxiang Luo1,2
1Department of Microbiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA
2Department of Microbiology, Peking University Health Science Center School of Basic Medical Sciences, Beijing, 100191, China
3Current address: Department of Pathology and Laboratory Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA
*These authors have contributed equally to this work
Keywords: hepatocellular carcinoma; hepatitis virus; tumorigenicity; proteomics; HCC targets
Received: February 18, 2017 Accepted: July 18, 2017 Published: September 27, 2017
Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver. A more thorough understanding of HCC pathogenesis will provide novel targets for development of cancer drugs to effectively treat HCC. To further this goal, we carried out a proteomic profiling of HCC cell lines Huh-7.4 and Huh-7.5. These two cell lines were derived from subgenomic HCV RNA-replicating Huh-7 cells upon clearance of HCV RNA by antiviral drug treatment. Initially, the tumorigenicity of each cell line was determined and compared in parallel in the same immunedeficient mice. Strikingly, the Huh-7.4 cell line was able to induce tumors, whereas the Huh-7.5 cell line failed to do so, providing unique model systems for identifying cellular genes and pathways important for HCC development and progression. Subsequently, one-dimensional LC-MS/MS proteomic and bioinformatics analyses were performed in the hope of identifying unique cellular genes and pathways responsible for HCC tumorigenicity. Interestingly, a total of 130 cellular genes were found to be significantly up- or downregulated between these two cell lines (r>3 fold, P<0.001). Also, EIF (EIF2&4), mTOR/p70S6K, ERK5, and EGFR signaling pathways were significantly different. Overall, these results provide significant new information to shed light on the underlying biological processes involved in HCC development and progression.
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