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Mol Nutr Food Res. 2012 Aug;56(8):1259-69. doi: 10.1002/mnfr.201200117. Epub 2012 May 29.

MicroRNA profiling of carcinogen-induced rat colon tumors and the influence of dietary spinach.

Author information

  • 1Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.

Abstract

SCOPE:

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.

CONCLUSION:

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.

© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID:
22641368
[PubMed - indexed for MEDLINE]
PMCID:
PMC3762592
Free PMC Article

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