title: Soy Isoflavone Genistein-Mediated Downregulation of miR-155 Contributes to the Anticancer Effects of Genistein.
abstract: We previously reported that dietary genistein inhibits mammary tumor growth and metastasis of the highly metastatic MDA-MB-435 cancer cells in immunocompromised mice. The purpose herein was to characterize the role of the novel oncogenic microRNA (miRNA) miR-155 in the anticancer effects of genistein in metastatic breast cancer. The effect of genistein was determined on breast cancer cell viability, apoptosis, and expression of miR-155 and its targets. At low physiologically relevant concentrations, genistein inhibits cell viability and induces apoptosis in metastatic MDA-MB-435 and Hs578t breast cancer cells, without affecting the viability of nonmetastatic MCF-7 breast cancer cells. In parallel with reduced cell viability, miR-155 is downregulated, whereas proapoptotic and anticell proliferative miR-155 targets FOXO3, PTEN, casein kinase, and p27 are upregulated in MDA-MB-435 and Hs578t cells in response to genistein treatment. However, miR-155 levels remain unchanged in response to genistein in the MCF-7 cells. Ectopic expression of miR-155 in MDA-MB-435 and Hs578t cells decreases the effects of genistein on cell viability and abrogates the effects of genistein on apoptosis and expression of proapoptotic genes. Therefore, genistein-mediated downregulation of miR-155 contributes to the anticancer effects of genistein in metastatic breast cancer.
authors.affiliation: a Department of Biochemistry , School of Medicine, University of Puerto Rico Medical Sciences Campus , San Juan , Puerto Rico.
authors.forename: Columba
authors.initials: C
authors.lastname: de la Parra
authors.affiliation: b Department of Biochemistry , School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico and Department of Pathology and Laboratory Medicine, Universidad Central del Caribe , Bayamon , Puerto Rico.
authors.forename: Linette
authors.initials: L
authors.lastname: Castillo-Pichardo
authors.affiliation: c Department of Biochemistry , School of Medicine, University of Puerto Rico Medical Sciences Campus , San Juan , Puerto Rico.
authors.forename: Ailed
authors.initials: A
authors.lastname: Cruz-Collazo
authors.affiliation: d Department of Anatomy and Cell Biology , Universidad Central del Caribe , Bayamon , Puerto Rico.
authors.forename: Luis
authors.initials: L
authors.lastname: Cubano
authors.affiliation: e Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , Texas , USA.
authors.forename: Roxana
authors.initials: R
authors.lastname: Redis
authors.affiliation: e Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , Texas , USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: f Department of Biochemistry , School of Medicine, University of Puerto Rico Medical Sciences Campus , San Juan , Puerto Rico.
authors.forename: Suranganie
authors.initials: S
authors.lastname: Dharmawardhane
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000032:analysis*; D051059:PTEN Phosphohydrolase / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D019833:Genistein; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human