Dietary Manipulation of Oncogenic MicroRNA Expression in Human Rectal Mucosa: A Randomized Trial
| Autor: | Karen Humphreys, Graeme P. Young, Nicholas A. Kennedy, Richard K. Le Leu, David L. Topping, Jean M. Winter, Lynne Cobiac, Michael A. Conlon, Anthony R. Bird, Ying Hu, Michael Michael |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Citrus Cancer Research Starch Colorectal cancer Biopsy Maize starch chemistry.chemical_compound Cluster Analysis Intestinal Mucosa Resistant starch Regulation of gene expression Cross-Over Studies food and beverages Middle Aged Gene Expression Regulation Neoplastic Intestines Milk Oncology Biochemistry Multigene Family Red meat Female RNA Long Noncoding medicine.medical_specialty Meat food.ingredient Butyrate Biology Zea mays Beverages food Internal medicine microRNA Genetics medicine Animals Humans Aged Cell Proliferation Rectal Neoplasms Gene Expression Profiling medicine.disease Diet MicroRNAs Metabolism Endocrinology chemistry Amylose |
| Zdroj: | Cancer Prevention Research. 7:786-795 |
| ISSN: | 1940-6215 1940-6207 |
| Popis: | Author version made available in accordance with the publisher's policy. High red meat intake is associated with increased colorectal cancer (CRC) risk, while resistant starch is probably protective. Resistant starch fermentation produces butyrate, which can alter microRNA (miRNA) levels in CRC cells in vitro; effects of red meat and resistant starch on miRNA expression in vivo were unknown. This study examined whether a high red meat (HRM) diet altered miRNA expression in rectal mucosa tissue of healthy volunteers, and if supplementation with butyrylated resistant starch (HRM+HAMSB) modified this response. In a randomised cross-over design, twenty-three volunteers undertook four 4-week dietary interventions; an HRM diet (300 g/day lean red meat) and an HRM+HAMSB diet (HRM with 40 g/day butyrylated high amylose maize starch), preceded by an entry diet and separated by a washout. Faecal butyrate increased with the HRM+HAMSB diet. Levels of oncogenic mature miRNAs, including miR-17-92 cluster miRNAs and miR-21, increased in the rectal mucosa with the HRM diet, while the HRM+HAMSB diet restored miR-17-92 miRNAs, but not miR-21, to baseline levels. Elevated miR-17-92 and miR-21 in the HRM diet corresponded with increased cell proliferation, and a decrease in miR-17-92 target gene transcript levels, including CDKN1A. The oncogenic miR-17-92 cluster is differentially regulated by dietary factors that increase or decrease risk for CRC, and this may explain, at least in part, the respective risk profiles of high red meat and resistant starch. These findings support increased resistant starch consumption as a means of reducing risk associated with an HRM diet. |
| Databáze: | OpenAIRE |
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