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High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways
BACKGROUND: Numerous epidemiologic studies have found a close association between obesity and cancer. Dietary fat is a fundamental contributor to obesity and is a risk factor for cancer. Thus far, the impact of dietary olive oil on cancer development remains inconclusive, and little is known about i...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440132/ https://www.ncbi.nlm.nih.gov/pubmed/30922331 http://dx.doi.org/10.1186/s12944-019-1023-6 |
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author | Zhang, Xiaoyu Yang, Ping Luo, Xuan Su, Chunxiao Chen, Yao Zhao, Lei Wei, Li Zeng, Han Varghese, Zac Moorhead, John F. Ruan, Xiong Z. Chen, Yaxi |
author_facet | Zhang, Xiaoyu Yang, Ping Luo, Xuan Su, Chunxiao Chen, Yao Zhao, Lei Wei, Li Zeng, Han Varghese, Zac Moorhead, John F. Ruan, Xiong Z. Chen, Yaxi |
author_sort | Zhang, Xiaoyu |
collection | PubMed |
description | BACKGROUND: Numerous epidemiologic studies have found a close association between obesity and cancer. Dietary fat is a fundamental contributor to obesity and is a risk factor for cancer. Thus far, the impact of dietary olive oil on cancer development remains inconclusive, and little is known about its underlying mechanisms. METHODS: Nude mouse xenograft models were used to examine the effects of high olive oil diet feeding on cervical cancer (CC) development and progression. Cell proliferation, migration and invasion were observed by the methods of EdU incorporation, Wound healing and Transwell assay, separately. RNA-sequencing technology and comprehensive bioinformatics analyses were used to elucidate the molecular processes regulated by dietary fat. Differentially expressed genes (DEGs) were identified and were functionally analyzed by Gene Ontology (GO), Kyoto Enrichment of Genes and Genomes (KEGG). Then, protein–protein interaction (PPI) network and sub-PPI network analyses were conducted using the STRING database and Cytoscape software. RESULTS: A high olive oil diet aggravated tumourigenesis in an experimental xenograft model of CC. Oleic acid, the main ingredient of olive oil, promoted cell growth and migration in vitro. Transcriptome sequencing analysis of xenograft tumour tissues was then performed to elucidate the regulation of molecular events regulated by dietary fat. Dietary olive oil induced 648 DEGs, comprising 155 up-regulated DEGs and 493 down-regulated DEGs. GO and pathway enrichment analysis revealed that some of the DEGs including EGR1 and FOXN2 were involved in the transcription regulation and others, including TGFB2 and COL4A3 in cell proliferation. The 15 most strongly associated DEGs were selected from the PPI network and hub genes including JUN, TIMP3, OAS1, OASL and EGR1 were confirmed by real-time quantitative PCR analysis. CONCLUSIONS: Our study suggests that a high olive oil diet aggravates CC progression in vivo and in vitro. We provide clues to build a potential link between dietary fat and cancerogenesis and identify areas requiring further investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12944-019-1023-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6440132 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64401322019-04-11 High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways Zhang, Xiaoyu Yang, Ping Luo, Xuan Su, Chunxiao Chen, Yao Zhao, Lei Wei, Li Zeng, Han Varghese, Zac Moorhead, John F. Ruan, Xiong Z. Chen, Yaxi Lipids Health Dis Research BACKGROUND: Numerous epidemiologic studies have found a close association between obesity and cancer. Dietary fat is a fundamental contributor to obesity and is a risk factor for cancer. Thus far, the impact of dietary olive oil on cancer development remains inconclusive, and little is known about its underlying mechanisms. METHODS: Nude mouse xenograft models were used to examine the effects of high olive oil diet feeding on cervical cancer (CC) development and progression. Cell proliferation, migration and invasion were observed by the methods of EdU incorporation, Wound healing and Transwell assay, separately. RNA-sequencing technology and comprehensive bioinformatics analyses were used to elucidate the molecular processes regulated by dietary fat. Differentially expressed genes (DEGs) were identified and were functionally analyzed by Gene Ontology (GO), Kyoto Enrichment of Genes and Genomes (KEGG). Then, protein–protein interaction (PPI) network and sub-PPI network analyses were conducted using the STRING database and Cytoscape software. RESULTS: A high olive oil diet aggravated tumourigenesis in an experimental xenograft model of CC. Oleic acid, the main ingredient of olive oil, promoted cell growth and migration in vitro. Transcriptome sequencing analysis of xenograft tumour tissues was then performed to elucidate the regulation of molecular events regulated by dietary fat. Dietary olive oil induced 648 DEGs, comprising 155 up-regulated DEGs and 493 down-regulated DEGs. GO and pathway enrichment analysis revealed that some of the DEGs including EGR1 and FOXN2 were involved in the transcription regulation and others, including TGFB2 and COL4A3 in cell proliferation. The 15 most strongly associated DEGs were selected from the PPI network and hub genes including JUN, TIMP3, OAS1, OASL and EGR1 were confirmed by real-time quantitative PCR analysis. CONCLUSIONS: Our study suggests that a high olive oil diet aggravates CC progression in vivo and in vitro. We provide clues to build a potential link between dietary fat and cancerogenesis and identify areas requiring further investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12944-019-1023-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-28 /pmc/articles/PMC6440132/ /pubmed/30922331 http://dx.doi.org/10.1186/s12944-019-1023-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zhang, Xiaoyu Yang, Ping Luo, Xuan Su, Chunxiao Chen, Yao Zhao, Lei Wei, Li Zeng, Han Varghese, Zac Moorhead, John F. Ruan, Xiong Z. Chen, Yaxi High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways |
title | High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways |
title_full | High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways |
title_fullStr | High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways |
title_full_unstemmed | High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways |
title_short | High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways |
title_sort | high olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440132/ https://www.ncbi.nlm.nih.gov/pubmed/30922331 http://dx.doi.org/10.1186/s12944-019-1023-6 |
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