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Exploring metabolic consequences of CPS1 and CAD dysregulation in hepatocellular carcinoma by network reconstruction

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Title: Exploring metabolic consequences of CPS1 and CAD dysregulation in hepatocellular carcinoma by network reconstruction
Authors: Dumenci, O
U, AMR
Khan, S
Holmes, E
Taylor-Robinson, S
Item Type: Journal Article
Abstract: Purpose: Hepatocellular carcinoma (HCC) is the fourth commonest cause of cancer-related mortality; it is associated with various genetic alterations, some involved in metabolic reprogramming. This study aimed to explore the potential metabolic impact of Carbamoyl Phosphate Synthase I (CPS1) and carbamoyl phosphate synthetase/aspartate transcarbamoylase/dihydroorotase (CAD) dysregulation through the reconstruction of a network that integrates information from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Human Metabolome Database (HMDB) and Human Protein Atlas (HPA). Methods and Results: Existing literature was used to determine the roles of CPS1 and CAD in HCC. CPS1 downregulation is thought to play a role in hepatocarcinogenesis through an increased glutamine availability for de novo pyrimidine biosynthesis, which CAD catalyzes the first three steps for. KEGG, HMDB and HPA were used to reconstruct a network of relevant pathways, demonstrating the relationships between genes and metabolites using the MetaboSignal package in R. The network was filtered to exclude any duplicates, and those greater than three steps away from CPS1 or CAD. Consequently, a network of 18 metabolites, 28 metabolic genes and 1 signaling gene was obtained, which indicated expression profiles and prognostic information of each gene in the network. Conclusion: Information from different databases was collated to form an informative network that integrated different ‘-omics’ approaches, demonstrating the relationships between genetic and metabolic components of urea cycle and the de novo pyrimidine biosynthesis pathway. This study paves the way for further research by acting as a template to investigate the relationships between genes and metabolites, explore their potential roles in various diseases and aid the development of new screening and treatment methods through network reconstruction.
Issue Date: 7-Jan-2020
Date of Acceptance: 20-Dec-2019
URI: http://hdl.handle.net/10044/1/75739
DOI: 10.2147/JHC.S239039
ISSN: 2253-5969
Publisher: Dove Medical Press
Start Page: 1
End Page: 9
Journal / Book Title: Journal of Hepatocellular Carcinoma
Volume: 7
Copyright Statement: © 2020 Dumenci et al. This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License. The full terms of the License are available at http://creativecommons.org/licenses/by/4.0/. The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
metabonomics
reprogramming
bioinformatics
liquid biopsy
hepatocytes
GENE
bioinformatics
hepatocytes
liquid biopsy
metabonomics
reprogramming
Publication Status: Published
Online Publication Date: 2020-01-07
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Electrical and Electronic Engineering
Faculty of Medicine
Faculty of Engineering