Folic Acid Induces Intake-Related Changes in the Mammary Tissue Transcriptome of C57BL/6 Mice
Autor: | Elie Antoun, Reyna S Penailillo, Mark Burton, Graham C. Burdge, Karen A. Lillycrop |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty mammary gland Mammary gland lcsh:TX341-641 Biology medicine.disease_cause Article Metastasis Transcriptome Mice 03 medical and health sciences folic acid Mammary Glands Animal 0302 clinical medicine breast cancer Downregulation and upregulation Internal medicine medicine Animals Epigenetics EZH2 Nutrition and Dietetics medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure 030220 oncology & carcinogenesis Histone methyltransferase Models Animal Female Carcinogenesis lcsh:Nutrition. Foods and food supply transcriptome Food Science |
Zdroj: | Nutrients Volume 12 Issue 9 Nutrients, Vol 12, Iss 2821, p 2821 (2020) |
ISSN: | 2072-6643 |
DOI: | 10.3390/nu12092821 |
Popis: | Folic acid (FA) intake has been associated with increased breast cancer risk in some studies. Although underlying mechanisms are unknown, epigenetic modifications that persistently alter transcription have been suggested. We tested the hypothesis that high FA (HFA) intake alters the adult mammary transcriptome in a manner consistent with increased potential for carcinogenesis, detectable beyond the period of intake. C57BL/6 mice were fed control FA (CFA) (1 mg/kg diet) or HFA (5 mg/kg diet) diets for 4 weeks, followed by AIN93M maintenance diet for 4 weeks. Plasma 5-methyltetrahydrofolate, p-aminobenzoylglutamate and unmetabolised FA concentrations were greater (1.62, 1.56, 5.80-fold, respectively) in HFA compared to CFA mice. RNA sequencing of the mammary transcriptome (~20 million reads) showed 222 transcripts (191 upregulated) differentially expressed between groups. Gene Set Enrichment showed upregulated genes significantly enriched in Epithelial Mesenchymal Transition, Myogenesis and Apical Junction and downregulated genes in E2F targets, MYC targets and G2M checkpoint. Cancer was the most altered Disease and Disorder pathway, with Metastasis, Mammary Tumour and Growth of Tumour the most upregulated pathways. ChIP-seq enrichment analysis showed that targets of histone methyltransferase EZH2 were enriched in HFA mice. This study demonstrates HFA intake during adulthood induces mammary transcriptome changes, consistent with greater tumorigenic potential. |
Databáze: | OpenAIRE |
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