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Carcinogenesis Advance Access published online on October 13, 2009
Carcinogenesis, doi:10.1093/carcin/bgp245
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

n-3 polyunsaturated fatty acids modulate carcinogen-directed non-coding microRNA signatures in rat colon

Laurie A. Davidson1,6, Naisyin Wang2, Manasvi S. Shah1,3, Joanne R. Lupton1,6, Ivan Ivanov4,6 and Robert S. Chapkin1,3,5,6

1 Program in Integrative Nutrition & Complex Diseases
2 Department of Statistics
3 Intercollegiate Faculty of Genetics
4 Department of Veterinary Physiology & Pharmacology
5 Vegetable and Fruit Improvement Center
6 Center for Environmental and Rural Health, Texas A&M University, College Station, TX 77843

* Address correspondence to Dr. Robert S. Chapkin, Faculty of Nutrition, 218 Kleberg Biotechnology Center, MS 2253, Texas A&M University, College Station TX 77843-2253, USA; Tel: 979-845-0419; Fax: 979-862-2378; E-mail: r-chapkin{at}tamu.edu

We have hypothesized that dietary modulation of intestinal non-coding RNA (microRNA) expression may contribute to the chemo-protective effects of nutritional bioactives (fish oil, pectin). To fully understand the effects of these agents on the expression of microRNAs, Sprague Dawley rats were fed diets containing corn oil or fish oil with pectin or cellulose and injected with azoxymethane (AOM, a colon-specific carcinogen) or saline (control). Real time PCR using microRNA specific primers and Taq ManTM probes was carried out to quantify effects on microRNA expression in colonic mucosa. From 368 mature microRNAs assayed, at an early stage of cancer progression (10 wk post AOM injection), let-7d, miR-15b, miR-107, miR-191 and miR-324-5p were significantly (p<0.05) affected by diet x carcinogen interactions. Overall, fish oil fed animals exhibited the smallest number of differentially expressed microRNAs (AOM vs saline treatment). With respect to the tumor stage (34 wk post AOM injection), 46 microRNAs were dysregulated in adenocarcinomas compared to normal mucosa from saline-injected animals. Of the 27 microRNAs expressed at higher (p<0.05) levels in tumors, miR-34a, 132, 223, and 224 were over expressed at greater than 10-fold. In contrast, the expression levels of miR-192, 194, 215, and 375 were dramatically reduced (0.32-fold or lower) in adenocarcinomas. These results demonstrate for the first time the utility of the rat AOM model, and the novel role of fish oil in protecting the colon from carcinogen-induced microRNA dysregulation.

Key Words: colon cancer • chemoprevention • micorRNA • Diet

Received April 6, 2009; revised September 4, 2009; accepted September 30, 2009.


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