Comparison of gene expression in liver regeneration and hepatocellular carcinoma formation

Li Yin,1–3 Yahao Wang,1,2 Xueqiang Guo,1,2 Cunshuan Xu,1,2 Guoying Yu1,2 1College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China; 2State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Engineering Laboratory for Bioengineering...

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Main Authors: Yin L, Wang Y, Guo X, Xu C, Yu G
Format: Article
Language:English
Published: Dove Medical Press 2018-11-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/comparison-of-gene-expression-in-liver-regeneration-and-hepatocellular-peer-reviewed-article-CMAR
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author Yin L
Wang Y
Guo X
Xu C
Yu G
author_facet Yin L
Wang Y
Guo X
Xu C
Yu G
author_sort Yin L
collection DOAJ
description Li Yin,1–3 Yahao Wang,1,2 Xueqiang Guo,1,2 Cunshuan Xu,1,2 Guoying Yu1,2 1College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China; 2State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Engineering Laboratory for Bioengineering and Drug Development, Henan Normal University, Xinxiang, Henan 453007, China; 3Laboratory of Tropical Biomedicine and Biotechnology, School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou 571199, China Background: Liver -cell proliferation occurs in hepatocellular carcinoma (HCC) and liver regeneration (LR). The development and progression of HCC and LR have many similar molecular pathways with very different results. In simple terms, LR is a controllable process of organ recovery and function reconstruction, whereas liver cancer is uncontrollable. Do they share common key pathways and genes? Methods: In this study, the dynamic transcriptome profile at ten time points (0, 2, 6, 12, 24, 30, 36, 72, 120, and 168 hours) during LR in rats after two-thirds hepatectomy and eight stages (normal, cirrhosis without HCC, cirrhosis, low-grade dysplastic, high-grade dysplastic, and very early, early advanced, and very advanced HCC) representing a stepwise carcinogenic process from preneoplastic lesions to end-stage HCC were analyzed in detail. A variety of bioinformatic methods, including MaSigPro, weighted gene-coexpression network analysis, and spatial analysis of functional enrichment, were used to analyze, elucidate, and compare similarities and differences between LR and HCC formation. Results: Key biological processes and genes were identified. From the comparison, we found that cell proliferation and angiogenesis were the most significantly dysregulated processes shared by LR and HCC. The pattern of cell-proliferation-related gene expression in progression stage during LR is similar to the transition process from dysplasia to early-stage HCC. LR and HCC showed different expression patterns as a whole. Some key genes, including FYN, XPO1, FOXM1, EZH2, and NRF1, were identified as playing critical roles in both LR and HCC. Conclusion: These findings could contribute to revealing the molecular mechanism of development and regulation mechanism of normal and abnormal proliferation, which could provide new ideas and treatment methods for regenerative medicine, oncological drug development, and oncological treatment. Keywords: liver regeneration, hepatocellular carcinoma, angiogenesis, MaSigPro, microarray, FYN
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spelling doaj.art-7fbeb570e52f448f96dfdd0d8891a18b2022-12-21T23:41:28ZengDove Medical PressCancer Management and Research1179-13222018-11-01Volume 105691570842314Comparison of gene expression in liver regeneration and hepatocellular carcinoma formationYin LWang YGuo XXu CYu GLi Yin,1–3 Yahao Wang,1,2 Xueqiang Guo,1,2 Cunshuan Xu,1,2 Guoying Yu1,2 1College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China; 2State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Engineering Laboratory for Bioengineering and Drug Development, Henan Normal University, Xinxiang, Henan 453007, China; 3Laboratory of Tropical Biomedicine and Biotechnology, School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou 571199, China Background: Liver -cell proliferation occurs in hepatocellular carcinoma (HCC) and liver regeneration (LR). The development and progression of HCC and LR have many similar molecular pathways with very different results. In simple terms, LR is a controllable process of organ recovery and function reconstruction, whereas liver cancer is uncontrollable. Do they share common key pathways and genes? Methods: In this study, the dynamic transcriptome profile at ten time points (0, 2, 6, 12, 24, 30, 36, 72, 120, and 168 hours) during LR in rats after two-thirds hepatectomy and eight stages (normal, cirrhosis without HCC, cirrhosis, low-grade dysplastic, high-grade dysplastic, and very early, early advanced, and very advanced HCC) representing a stepwise carcinogenic process from preneoplastic lesions to end-stage HCC were analyzed in detail. A variety of bioinformatic methods, including MaSigPro, weighted gene-coexpression network analysis, and spatial analysis of functional enrichment, were used to analyze, elucidate, and compare similarities and differences between LR and HCC formation. Results: Key biological processes and genes were identified. From the comparison, we found that cell proliferation and angiogenesis were the most significantly dysregulated processes shared by LR and HCC. The pattern of cell-proliferation-related gene expression in progression stage during LR is similar to the transition process from dysplasia to early-stage HCC. LR and HCC showed different expression patterns as a whole. Some key genes, including FYN, XPO1, FOXM1, EZH2, and NRF1, were identified as playing critical roles in both LR and HCC. Conclusion: These findings could contribute to revealing the molecular mechanism of development and regulation mechanism of normal and abnormal proliferation, which could provide new ideas and treatment methods for regenerative medicine, oncological drug development, and oncological treatment. Keywords: liver regeneration, hepatocellular carcinoma, angiogenesis, MaSigPro, microarray, FYNhttps://www.dovepress.com/comparison-of-gene-expression-in-liver-regeneration-and-hepatocellular-peer-reviewed-article-CMARliver regenerationhepatocellular carcinomaangiogenesismaSigPromicroarrayFYN
spellingShingle Yin L
Wang Y
Guo X
Xu C
Yu G
Comparison of gene expression in liver regeneration and hepatocellular carcinoma formation
Cancer Management and Research
liver regeneration
hepatocellular carcinoma
angiogenesis
maSigPro
microarray
FYN
title Comparison of gene expression in liver regeneration and hepatocellular carcinoma formation
title_full Comparison of gene expression in liver regeneration and hepatocellular carcinoma formation
title_fullStr Comparison of gene expression in liver regeneration and hepatocellular carcinoma formation
title_full_unstemmed Comparison of gene expression in liver regeneration and hepatocellular carcinoma formation
title_short Comparison of gene expression in liver regeneration and hepatocellular carcinoma formation
title_sort comparison of gene expression in liver regeneration and hepatocellular carcinoma formation
topic liver regeneration
hepatocellular carcinoma
angiogenesis
maSigPro
microarray
FYN
url https://www.dovepress.com/comparison-of-gene-expression-in-liver-regeneration-and-hepatocellular-peer-reviewed-article-CMAR
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AT xuc comparisonofgeneexpressioninliverregenerationandhepatocellularcarcinomaformation
AT yug comparisonofgeneexpressioninliverregenerationandhepatocellularcarcinomaformation