eprintid: 10072454
rev_number: 16
eprint_status: archive
userid: 608
dir: disk0/10/07/24/54
datestamp: 2019-04-25 15:28:39
lastmod: 2021-10-15 22:41:17
status_changed: 2019-04-25 15:28:39
type: article
metadata_visibility: show
creators_name: Zhang, X
creators_name: Yang, P
creators_name: Luo, X
creators_name: Su, C
creators_name: Chen, Y
creators_name: Zhao, L
creators_name: Wei, L
creators_name: Zeng, H
creators_name: Varghese, Z
creators_name: Moorhead, JF
creators_name: Ruan, XZ
creators_name: Chen, Y
title: High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G93
keywords: High olive oil diet, Cervical cancer, Transcriptome analysis; differentially expressed genes
note: This article is distributed under the terms of the Creative Commons Attribution 4.0
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abstract: 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.
date: 2019-03-28
date_type: published
official_url: https://doi.org/10.1186/s12944-019-1023-6
oa_status: green
full_text_type: pub
pmcid: PMC6440132
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1646145
doi: 10.1186/s12944-019-1023-6
pii: 10.1186/s12944-019-1023-6
lyricists_name: Ruan, Xiong-Zhong
lyricists_id: XZRUA13
actors_name: Cuccu, Clara
actors_id: CCCUC40
actors_role: owner
full_text_status: public
publication: Lipids in Health and Disease
volume: 18
article_number: 76
event_location: England
issn: 1476-511X
citation:        Zhang, X;    Yang, P;    Luo, X;    Su, C;    Chen, Y;    Zhao, L;    Wei, L;                     ... Chen, Y; + view all <#>        Zhang, X;  Yang, P;  Luo, X;  Su, C;  Chen, Y;  Zhao, L;  Wei, L;  Zeng, H;  Varghese, Z;  Moorhead, JF;  Ruan, XZ;  Chen, Y;   - view fewer <#>    (2019)    High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways.                   Lipids in Health and Disease , 18     , Article 76.  10.1186/s12944-019-1023-6 <https://doi.org/10.1186/s12944-019-1023-6>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10072454/1/Zhang_s12944-019-1023-6.pdf