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

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
Molecular Nutrition & Food Research (Impact Factor: 4.6). 08/2012; 56(8):1259-69. DOI: 10.1002/mnfr.201200117
Source: PubMed


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.
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.

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Available from: Roderick Dashwood, Oct 07, 2015
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    • "Loss of let-7a, and of other let-7 family members, coincided with changes in other high-abundance miRNAs in the heterocyclic amine-induced rat colon tumors examined here [24]. Interestingly, however, when the dataset of 679 miRNAs was taken in its entirety, the low-abundance miR-206 was identified as the most significantly upregulated (up to 73-fold) in rat colon tumors relative to normal colonic mucosa. "
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