MicroRNA profiling of carcinogen-induced rat colon tumors and the influence of dietary spinach
Version of Record online: 29 MAY 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 56, Issue 8, pages 1259–1269, August 2012
How to Cite
Parasramka, M. A., Dashwood, W. M., Wang, R., Abdelli, A., Bailey, G. S., Williams, D. E., Ho, E. and Dashwood, R. H. (2012), MicroRNA profiling of carcinogen-induced rat colon tumors and the influence of dietary spinach. Mol. Nutr. Food Res., 56: 1259–1269. doi: 10.1002/mnfr.201200117
- Issue online: 10 AUG 2012
- Version of Record online: 29 MAY 2012
- Manuscript Accepted: 3 APR 2012
- Manuscript Revised: 22 MAR 2012
- Manuscript Received: 21 FEB 2012
- NIH. Grant Numbers: CA090890, CA122959, CA90176, P30 ES00210
- EHSC Pilot Project
- Colon cancer;
- Pluripotent factors
MicroRNA (miRNA) profiles are altered in chronic conditions such as cardiovascular disease, diabetes, neurological disorders, and cancer. A systems biology approach was used to examine, for the first time, miRNAs altered in rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine carcinogen from cooked meat.
Methods and results
Among the most highly dysregulated miRNAs were those belonging to the let-7 family. Subsequent computational modeling and target validation identified c-Myc and miRNA-binding proteins Lin28A/Lin28B (Lin28) as key players, along with Sox2, Nanog, and Oct-3/4. These targets of altered miRNAs in colon cancers have been implicated in tumor recurrence and reduced patient survival, in addition to their role as pluripotency factors. In parallel with these findings, the tumor-suppressive effects of dietary spinach given postinitiation correlated with elevated levels of let-7 family members and partial normalization of c-myc, Sox2, Nanog, Oct-3/4, HmgA2, Dnmt3b, and P53 expression.
We conclude that the let-7/c-Myc/Lin28 axis is dysregulated in heterocyclic amine-induced colon carcinogenesis, and that the tumor suppressive effects of dietary spinach are associated with partial normalization of this pathway.