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Integrated omics and gene expression analysis identifies the loss of metabolite–metabolite correlations in small cell lung cancer
BACKGROUND AND OBJECTIVE: Small cell lung cancer (SCLC) is the most aggressive type of lung carcinoma with high metastatic potential and chemoresistance upon relapse. Cancer cells remodel the existing metabolic pathways for their benefits and the perturbations in cellular metabolism are the hallmark...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039056/ https://www.ncbi.nlm.nih.gov/pubmed/30013371 http://dx.doi.org/10.2147/OTT.S166149 |
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author | Yu, Li Li, Kefeng Xu, Zhaoguo Cui, Guoyuan Zhang, Xiaoye |
author_facet | Yu, Li Li, Kefeng Xu, Zhaoguo Cui, Guoyuan Zhang, Xiaoye |
author_sort | Yu, Li |
collection | PubMed |
description | BACKGROUND AND OBJECTIVE: Small cell lung cancer (SCLC) is the most aggressive type of lung carcinoma with high metastatic potential and chemoresistance upon relapse. Cancer cells remodel the existing metabolic pathways for their benefits and the perturbations in cellular metabolism are the hallmark of cancer. However, the extent of these changes remains largely unknown for SCLC. MATERIALS AND METHODS: We characterized the metabolic perturbations in SCLC cells (SCLCC) by metabolomics. Large-scale correlation analysis was performed between metabolites. Targeted proteomics and gene expression analysis were employed to investigate the changes of key enzymes and genes in the disturbed pathways. RESULTS: We found dramatic decrease of metabolite–metabolite correlations in SCLCC compared with normal control cells and non-small cell lung cancer cells. Pathway analysis revealed that the loss of correlations was associated with the alternations of fatty acid oxidation, urea cycle, and purine salvage pathway in SCLCC. Targeted proteomics and gene expression analysis confirmed significant changes of the expression for the key enzymes and genes in the pathways in SCLCC including the upregulation of carbamoyl phosphate synthase 1 (urea cycle) and carnitine palmitoyltransferase 1A (fatty acid oxidation), and the downregulation of hypoxanthine–guanine phosphoribosyltransferase and adenine phosphoribosyltransferase in purine salvage pathway. CONCLUSION: We demonstrated the loss of metabolite–metabolite correlations in SCLCC associated with the upregulation of fatty acid oxidation and urea cycle and the downregulation of purine salvage pathways. Our findings provide insights into the metabolic reprogramming in SCLCC and highlight the potential therapeutic targets for the treatment of SCLC. |
format | Online Article Text |
id | pubmed-6039056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60390562018-07-16 Integrated omics and gene expression analysis identifies the loss of metabolite–metabolite correlations in small cell lung cancer Yu, Li Li, Kefeng Xu, Zhaoguo Cui, Guoyuan Zhang, Xiaoye Onco Targets Ther Original Research BACKGROUND AND OBJECTIVE: Small cell lung cancer (SCLC) is the most aggressive type of lung carcinoma with high metastatic potential and chemoresistance upon relapse. Cancer cells remodel the existing metabolic pathways for their benefits and the perturbations in cellular metabolism are the hallmark of cancer. However, the extent of these changes remains largely unknown for SCLC. MATERIALS AND METHODS: We characterized the metabolic perturbations in SCLC cells (SCLCC) by metabolomics. Large-scale correlation analysis was performed between metabolites. Targeted proteomics and gene expression analysis were employed to investigate the changes of key enzymes and genes in the disturbed pathways. RESULTS: We found dramatic decrease of metabolite–metabolite correlations in SCLCC compared with normal control cells and non-small cell lung cancer cells. Pathway analysis revealed that the loss of correlations was associated with the alternations of fatty acid oxidation, urea cycle, and purine salvage pathway in SCLCC. Targeted proteomics and gene expression analysis confirmed significant changes of the expression for the key enzymes and genes in the pathways in SCLCC including the upregulation of carbamoyl phosphate synthase 1 (urea cycle) and carnitine palmitoyltransferase 1A (fatty acid oxidation), and the downregulation of hypoxanthine–guanine phosphoribosyltransferase and adenine phosphoribosyltransferase in purine salvage pathway. CONCLUSION: We demonstrated the loss of metabolite–metabolite correlations in SCLCC associated with the upregulation of fatty acid oxidation and urea cycle and the downregulation of purine salvage pathways. Our findings provide insights into the metabolic reprogramming in SCLCC and highlight the potential therapeutic targets for the treatment of SCLC. Dove Medical Press 2018-07-06 /pmc/articles/PMC6039056/ /pubmed/30013371 http://dx.doi.org/10.2147/OTT.S166149 Text en © 2018 Yu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Yu, Li Li, Kefeng Xu, Zhaoguo Cui, Guoyuan Zhang, Xiaoye Integrated omics and gene expression analysis identifies the loss of metabolite–metabolite correlations in small cell lung cancer |
title | Integrated omics and gene expression analysis identifies the loss of metabolite–metabolite correlations in small cell lung cancer |
title_full | Integrated omics and gene expression analysis identifies the loss of metabolite–metabolite correlations in small cell lung cancer |
title_fullStr | Integrated omics and gene expression analysis identifies the loss of metabolite–metabolite correlations in small cell lung cancer |
title_full_unstemmed | Integrated omics and gene expression analysis identifies the loss of metabolite–metabolite correlations in small cell lung cancer |
title_short | Integrated omics and gene expression analysis identifies the loss of metabolite–metabolite correlations in small cell lung cancer |
title_sort | integrated omics and gene expression analysis identifies the loss of metabolite–metabolite correlations in small cell lung cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039056/ https://www.ncbi.nlm.nih.gov/pubmed/30013371 http://dx.doi.org/10.2147/OTT.S166149 |
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