|Title||MicroRNA profiling of carcinogen-induced rat colon tumors and the influence of dietary spinach.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Parasramka MA, W Dashwood M, Wang R, Abdelli A, Bailey GS, Williams DE, Ho E, Dashwood RH|
|Journal||Mol Nutr Food Res|
|Date Published||2012 Aug|
|Keywords||Animals, Carcinogens, Colonic Neoplasms, Computer Simulation, Gene Expression Regulation, Neoplastic, Imidazoles, Male, MicroRNAs, Rats, Rats, Inbred F344, RNA-Binding Proteins, Spinacia oleracea|
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.
|Alternate Journal||Mol Nutr Food Res|
|PubMed Central ID||PMC3762592|
|Grant List||CA122959 / CA / NCI NIH HHS / United States |
P01 CA090890 / CA / NCI NIH HHS / United States
P30 ES00210 / ES / NIEHS NIH HHS / United States
R01 CA080176 / CA / NCI NIH HHS / United States
R29 CA065525 / CA / NCI NIH HHS / United States
CA090890 / CA / NCI NIH HHS / United States
R01 CA065525 / CA / NCI NIH HHS / United States
CA90176 / CA / NCI NIH HHS / United States
R01 CA122959 / CA / NCI NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States