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Article: Mechanistic insights into zearalenone-accelerated colorectal cancer in mice using integrative multi-omics approaches

TitleMechanistic insights into zearalenone-accelerated colorectal cancer in mice using integrative multi-omics approaches
Authors
Issue Date1-Feb-2023
PublisherElsevier
Citation
Computational and Structural Biotechnology Journal, 2023, v. 21, p. 1785-1796 How to Cite?
Abstract

Zearalenone (ZEA), a secondary metabolite of Fusarium fungi found in cereal-based foods, promotes the growth of colon, breast, and prostate cancer cells in vitro. However, the lack of animal studies hinders a deeper mechanistic understanding of the cancer-promoting effects of ZEA. This study aimed to determine the effect of ZEA on colon cancer progression and its underlying mechanisms. Through integrative analyses of transcriptomicsmetabolomicsmetagenomics, and host phenotypes, we investigated the impact of a 4-week ZEA intervention on colorectal cancer in xenograft mice. Our results showed a twofold increase in tumor weight with the 4-week ZEA intervention. ZEA exposure significantly increased the mRNA and protein levels of BEST4, DGKB, and Ki67 and the phosphorylation levels of ERK1/2 and AKT. Serum metabolomic analysis revealed that the levels of amino acids, including histidine, arginine, citrulline, and glycine, decreased significantly in the ZEA group. Furthermore, ZEA lowered the alpha diversity of the gut microbiota and reduced the abundance of nine genera, including Tuzzerella and Rikenella. Further association analysis indicated that Tuzzerella was negatively associated with the expression of BEST4 and DGKB genes, serum uric acid levels, and tumor weight. Additionally, circulatory hippuric acid levels positively correlated with tumor weight and the expression of oncogenic genes, including ROBO3, JAK3, and BEST4. Altogether, our results indicated that ZEA promotes colon cancer progression by enhancing the BEST4/AKT/ERK1/2 pathway, lowering circulatory amino acid concentrations, altering gut microbiota composition, and suppressing short chain fatty acids production.


Persistent Identifierhttp://hdl.handle.net/10722/328360
ISSN
2023 Impact Factor: 4.4
2023 SCImago Journal Rankings: 1.485

 

DC FieldValueLanguage
dc.contributor.authorLo, EKK-
dc.contributor.authorWang, XW-
dc.contributor.authorLee, PK-
dc.contributor.authorWong, HC-
dc.contributor.authorLee, JCY-
dc.contributor.authorGomez-Gallego, C-
dc.contributor.authorZhao, DY-
dc.contributor.authorEl-Nezami, H-
dc.contributor.authorLi, J -
dc.date.accessioned2023-06-28T04:43:16Z-
dc.date.available2023-06-28T04:43:16Z-
dc.date.issued2023-02-01-
dc.identifier.citationComputational and Structural Biotechnology Journal, 2023, v. 21, p. 1785-1796-
dc.identifier.issn2001-0370-
dc.identifier.urihttp://hdl.handle.net/10722/328360-
dc.description.abstract<p>Zearalenone (ZEA), a <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/secondary-metabolite" title="Learn more about secondary metabolite from ScienceDirect's AI-generated Topic Pages">secondary metabolite</a> of <em><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fusarium" title="Learn more about Fusarium from ScienceDirect's AI-generated Topic Pages">Fusarium</a></em> fungi found in cereal-based foods, promotes the growth of colon, breast, and prostate cancer cells in vitro. However, the lack of animal studies hinders a deeper mechanistic understanding of the cancer-promoting effects of ZEA. This study aimed to determine the effect of ZEA on colon cancer progression and its underlying mechanisms. Through integrative analyses of <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/transcriptomics" title="Learn more about transcriptomics from ScienceDirect's AI-generated Topic Pages">transcriptomics</a>, <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/metabolomics" title="Learn more about metabolomics from ScienceDirect's AI-generated Topic Pages">metabolomics</a>, <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/metagenomics" title="Learn more about metagenomics from ScienceDirect's AI-generated Topic Pages">metagenomics</a>, and host phenotypes, we investigated the impact of a 4-week ZEA intervention on colorectal cancer in xenograft mice. Our results showed a twofold increase in tumor weight with the 4-week ZEA intervention. ZEA exposure significantly increased the mRNA and protein levels of BEST4, DGKB, and Ki67 and the phosphorylation levels of ERK1/2 and AKT. Serum metabolomic analysis revealed that the levels of <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/amino-acids" title="Learn more about amino acids from ScienceDirect's AI-generated Topic Pages">amino acids</a>, including <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/histidine" title="Learn more about histidine from ScienceDirect's AI-generated Topic Pages">histidine</a>, arginine, <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/citrulline" title="Learn more about citrulline from ScienceDirect's AI-generated Topic Pages">citrulline</a>, and glycine, decreased significantly in the ZEA group. Furthermore, ZEA lowered the alpha diversity of the <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/intestine-flora" title="Learn more about gut microbiota from ScienceDirect's AI-generated Topic Pages">gut microbiota</a> and reduced the abundance of nine genera, including <em>Tuzzerella</em> and <em>Rikenella</em>. Further association analysis indicated that <em>Tuzzerella</em> was negatively associated with the expression of BEST4 and DGKB genes, <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/uric-acid-blood-level" title="Learn more about serum uric acid from ScienceDirect's AI-generated Topic Pages">serum uric acid</a> levels, and tumor weight. Additionally, circulatory hippuric acid levels positively correlated with tumor weight and the expression of <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/oncogene" title="Learn more about oncogenic genes from ScienceDirect's AI-generated Topic Pages">oncogenic genes</a>, including ROBO3, JAK3, and BEST4. Altogether, our results indicated that ZEA promotes colon cancer progression by enhancing the BEST4/AKT/ERK1/2 pathway, lowering circulatory amino acid concentrations, altering gut microbiota composition, and suppressing <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/short-chain-fatty-acid" title="Learn more about short chain fatty acids from ScienceDirect's AI-generated Topic Pages">short chain fatty acids</a> production.<br></p>-
dc.languageeng-
dc.publisherElsevier-
dc.relation.ispartofComputational and Structural Biotechnology Journal-
dc.titleMechanistic insights into zearalenone-accelerated colorectal cancer in mice using integrative multi-omics approaches-
dc.typeArticle-
dc.identifier.doi10.1016/j.csbj.2023.02.048-
dc.identifier.hkuros344678-
dc.identifier.volume21-
dc.identifier.spage1785-
dc.identifier.epage1796-
dc.identifier.eissn2001-0370-
dc.identifier.issnl2001-0370-

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