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Micro RNA profiling of carcinogen‐induced rat colon tumors and the influence of dietary spinach
Author(s) -
Parasramka Mansi A.,
Dashwood W. Mohaiza,
Wang Rong,
Abdelli Amir,
Bailey George S.,
Williams David E.,
Ho Emily,
Dashwood Roderick H.
Publication year - 2012
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200117
Subject(s) - rna , ipomoea aquatica , colorectal cancer , homeobox protein nanog , carcinogenesis , cancer research , spinach , carcinogen , lin28 , sox2 , biology , rna binding protein , chemistry , biochemistry , microbiology and biotechnology , cancer , medicine , transcription factor , embryonic stem cell , gene , induced pluripotent stem cell
Scope Micro RNA (mi RNA ) 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, mi RNA s 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 mi RNA s were those belonging to the let‐7 family. Subsequent computational modeling and target validation identified c‐Myc and mi RNA ‐binding proteins Lin28A/Lin28B (Lin28) as key players, along with Sox2, Nanog, and Oct‐3/4. These targets of altered mi RNA s 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.