title: Dietary walnut suppression of colorectal cancer in mice: Mediation by miRNA patterns and fatty acid incorporation.
abstract: Colorectal cancer, unlike many other malignancies, may be preventable. Recent studies have demonstrated an inverse association between nut consumption and incidence of colon cancer; however, the underlying mechanisms are not fully understood. An emerging concept suggests that microribonucleic acids (miRNAs) may help explain the relationship between walnut consumption and decreased colorectal neoplasia risk. Seven days after HT-29 colon cancer cell injection, mice were randomized to either control or walnut diets for 25 days of diet treatment. Thirty samples of tumor and of omental adipose were analyzed to determine changes in lipid composition in each dietary group. In the tumors of the walnut-containing diet, we found significant increases in α-linolenic, eicosapentaenoic, docosahexaenoic and total omega-3 acids, and a decrease in arachidonic acid, as compared to the control diet. Final tumor size measured at sacrifice was negatively associated with percentage of total omega-3 fatty acid composition (r=-0.641, P=.001). MicroRNA expression analysis of colorectal tumor tissue revealed decreased expression of miRNAs 1903, 467c and 3068 (P<.05) and increased expression of miRNA 297a* (P=.0059) in the walnut-treated group as compared to control diet. Our results indicate that changes in the miRNA expression profiles likely affect target gene transcripts involved in pathways of anti-inflammation, antivascularization, antiproliferation and apoptosis. We also demonstrate the incorporation of protective fatty acids into colonic epithelium of walnut-fed mice, which may independently alter miRNA expression profiles itself. Future studies of the mechanism of widespread miRNA regulation by walnut consumption are needed to offer potential prognostic and therapeutic targets.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Section of Endocrinology, Boston VA Healthcare system, Boston, MA. Electronic address: mtsouka1@bidmc.harvard.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tsoukas
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Byung-Joon
authors.initials: BJ
authors.lastname: Ko
authors.affiliation: Department of Biochemistry and Microbiology, Marshall University School of Medicine, Huntington, WV.
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Witte
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Fadime
authors.initials: F
authors.lastname: Dincer
authors.affiliation: Department of Biochemistry and Microbiology, Marshall University School of Medicine, Huntington, WV.
authors.forename: W Elaine
authors.initials: WE
authors.lastname: Hardman
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Section of Endocrinology, Boston VA Healthcare system, Boston, MA.
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D055951:Functional Food / Q000032:analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology; D031324:Juglans / Q000737:chemistry; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009754:Nuts / Q000737:chemistry; D011897:Random Allocation; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D015525:Fatty Acids, Omega-3; D035683:MicroRNAs
keywords: Angiogenesis; Anti-inflammation; Apoptosis; Colon cancer; Fatty acids; Walnut; miRNA