Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis

Hepatocellular carcinoma (HCC) has a high mortality rate and early detection of HCC is crucial for the application of effective treatment strategies. HCC is typically caused by either viral hepatitis infection or by fatty liver disease. To diagnose and treat HCC it is necessary to elucidate the unde...

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Main Authors:	Lee, Sunjae, Mardinoglu, Adil, Zhang, Cheng, Lee, Doheon, Nielsen, Jens
Format:	Online
Language:	English
Published:	Oxford University Press 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937331/

id	pubmed-4937331
recordtype	oai_dc
spelling	pubmed-49373312016-07-11 Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis Lee, Sunjae Mardinoglu, Adil Zhang, Cheng Lee, Doheon Nielsen, Jens Computational Biology Hepatocellular carcinoma (HCC) has a high mortality rate and early detection of HCC is crucial for the application of effective treatment strategies. HCC is typically caused by either viral hepatitis infection or by fatty liver disease. To diagnose and treat HCC it is necessary to elucidate the underlying molecular mechanisms. As a major cause for development of HCC is fatty liver disease, we here investigated anomalies in regulation of lipid metabolism in the liver. We applied a tailored network-based approach to identify signaling hubs associated with regulation of this part of metabolism. Using transcriptomics data of HCC patients, we identified significant dysregulated expressions of lipid-regulated genes, across many different lipid metabolic pathways. Our findings, however, show that viral hepatitis causes HCC by a distinct mechanism, less likely involving lipid anomalies. Based on our analysis we suggest signaling hub genes governing overall catabolic or anabolic pathways, as novel drug targets for treatment of HCC that involves lipid anomalies. Oxford University Press 2016-07-08 2016-05-23 /pmc/articles/PMC4937331/ /pubmed/27216817 http://dx.doi.org/10.1093/nar/gkw462 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lee, Sunjae Mardinoglu, Adil Zhang, Cheng Lee, Doheon Nielsen, Jens
spellingShingle	Lee, Sunjae Mardinoglu, Adil Zhang, Cheng Lee, Doheon Nielsen, Jens Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis
author_facet	Lee, Sunjae Mardinoglu, Adil Zhang, Cheng Lee, Doheon Nielsen, Jens
author_sort	Lee, Sunjae
title	Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis
title_short	Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis
title_full	Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis
title_fullStr	Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis
title_full_unstemmed	Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis
title_sort	dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis
description	Hepatocellular carcinoma (HCC) has a high mortality rate and early detection of HCC is crucial for the application of effective treatment strategies. HCC is typically caused by either viral hepatitis infection or by fatty liver disease. To diagnose and treat HCC it is necessary to elucidate the underlying molecular mechanisms. As a major cause for development of HCC is fatty liver disease, we here investigated anomalies in regulation of lipid metabolism in the liver. We applied a tailored network-based approach to identify signaling hubs associated with regulation of this part of metabolism. Using transcriptomics data of HCC patients, we identified significant dysregulated expressions of lipid-regulated genes, across many different lipid metabolic pathways. Our findings, however, show that viral hepatitis causes HCC by a distinct mechanism, less likely involving lipid anomalies. Based on our analysis we suggest signaling hub genes governing overall catabolic or anabolic pathways, as novel drug targets for treatment of HCC that involves lipid anomalies.
publisher	Oxford University Press
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937331/
_version_	1613605945110167552

Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis

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