Research Article

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

  1. Mansi A. Parasramka1,
  2. W. Mohaiza Dashwood1,
  3. Rong Wang1,
  4. Amir Abdelli1,
  5. George S. Bailey1,
  6. David E. Williams1,2,
  7. Emily Ho1,3,
  8. Roderick H. Dashwood1,2,*

Article first published online: 29 MAY 2012

DOI: 10.1002/mnfr.201200117

Issue

Molecular Nutrition & Food Research

Molecular Nutrition & Food Research

Volume 56, Issue 8, pages 1259–1269, August 2012

Additional Information

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

Author Information

  1. 1

    Linus Pauling Institute, Oregon State University, Corvallis, OR, USA

  2. 2

    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA

  3. 3

    School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA

* Correspondence: Dr. Roderick H. Dashwood, 479 Linus Pauling Science Center, Oregon State University, Corvallis, OR 97331, USA
E-mail: Rod.Dashwood@oregonstate.edu
Fax: +1-541-737-5077

Publication History

  1. Issue published online: 10 AUG 2012
  2. Article first published online: 29 MAY 2012
  3. Manuscript Accepted: 3 APR 2012
  4. Manuscript Revised: 22 MAR 2012
  5. Manuscript Received: 21 FEB 2012

Funded by

  • NIH. Grant Numbers: CA090890, CA122959, CA90176, P30 ES00210
  • EHSC Pilot Project

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Keywords:

  • Chemoprevention;
  • Colon cancer;
  • Epigenetics;
  • MicroRNAs;
  • Pluripotent factors

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.

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