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Identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling

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 H...

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Autores principales: Zamani, Ali, Fan, Huahao, Luo, Guangxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707090/
https://www.ncbi.nlm.nih.gov/pubmed/29221196
http://dx.doi.org/10.18632/oncotarget.21821
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author Zamani, Ali
Fan, Huahao
Luo, Guangxiang
author_facet Zamani, Ali
Fan, Huahao
Luo, Guangxiang
author_sort Zamani, Ali
collection PubMed
description 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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spelling pubmed-57070902017-12-07 Identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling Zamani, Ali Fan, Huahao Luo, Guangxiang Oncotarget Research Paper 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. Impact Journals LLC 2017-09-27 /pmc/articles/PMC5707090/ /pubmed/29221196 http://dx.doi.org/10.18632/oncotarget.21821 Text en Copyright: © 2017 Zamani et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zamani, Ali
Fan, Huahao
Luo, Guangxiang
Identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling
title Identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling
title_full Identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling
title_fullStr Identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling
title_full_unstemmed Identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling
title_short Identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling
title_sort identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707090/
https://www.ncbi.nlm.nih.gov/pubmed/29221196
http://dx.doi.org/10.18632/oncotarget.21821
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