High olive oil diets enhance cervical tumour growth in mice: transcriptome analysis for potential candidate genes and pathways

Xiaoyu Zhang,Li Wei,Han Zeng,Xiong Z Ruan,Yao Chen,Chunxiao Su,Lei Zhao,Zac Varghese,Ping Yang,Xuan Luo,John F Moorhead,Yaxi Chen

doi:10.1186/s12944-019-1023-6

Xiaoyu Zhang, Li Wei + Show 10 more

Open Access

https://doi.org/10.1186/s12944-019-1023-6

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Abstract

BackgroundNumerous 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.MethodsNude 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.ResultsA 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.ConclusionsOur 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.

Highlights

Numerous epidemiologic studies have found a close association between obesity and cancer
High olive oil diet promotes tumour growth in an experimental CC model HeLa cells were implanted subcutaneously to control diet (CD)- and OD-fed nude mice to address the effects of dietary olive oil on tumourigenesis
High olive oil diet markedly increased the weight of the xenografts by more than 6-fold (Fig. 1c)

Summary

Introduction

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. Progression from high-risk HPV-positive premalignant lesions to malignant carcinoma seldom occurs [4], indicating additional contributors are required to promote CC’s malignant transformation and progression. A large body of emerging evidence has elucidated a strong association between obesity and CC morbidity and mortality [5,6,7]. Dietary fat is a fundamental contributor to obesity [8, 9] and is one of the potential factors thought to link obesity and CC. Recent evidence has suggested that both amount and type of dietary fat are important in the cancer aetiology [13]

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