title: β-ionone modulates the expression of miRNAs and genes involved in the metastatic phenotype of microdissected persistent preneoplastic lesions in rats submitted to hepatocarcinogenesis.
abstract: MicroRNAs (miRNAs) are post-transcriptional gene expression regulators which expression is frequently altered in hepatocellular carcinoma (HCC). β-ionone (βI) is noted for its ability to inhibit persistent preneoplastic lesions (pPNLs) in liver rats. We evaluated the expression of miRNAs involved in carcinogenesis and possible targets modulated by βI, in pPNLs and surrounding of microdissected tissues. Rats subjected to resistant hepatocyte model were treated during promotion stage with βI (16 mg/100 g body weight) or corn oil (CO; 0.25 mL/100 g body weight; controls). Five animals receive no treatment (NT). In CO group, 38 and 29 miRNAs showed reduced expression relative to NT (P < 0.05) in pPNLs and surrounding, respectively. No miRNAs showed increased expression in surrounding of the CO compared to NT group; however, 30 miRNAs showed increased expression (P ≤ 0.05) in pPNLs of the CO group. There was no difference between βI and CO groups (P > 0.05) in the expression of miRNAs in surrounding. In pPNLs βI increased expression of miR-122 and miR-34a (P ≤ 0.05) and reduced of Igf2 (P ≤ 0.05), target of the latter, compared to CO. Additionally, βI decreased the expression of miR-181c and its target Gdf2 (P ≤ 0.05). βI reduced the expression of miR-181b and miR-708 (P ≤ 0.05) and increased the expression of their respective target mRNAs Timp3 and Mtss1 (P ≤ 0.05), relative to CO group. Modulation of miRNAs target genes by βI was confirmed in vitro. βI is a promising chemopreventive agent in the initial stages of hepatocarcinogenesis, as it modulates the expression of the miRNAs and target genes that can alter the metastatic phenotype of HCC. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratory of Diet, Nutrition, and Cancer, Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Kelly Silva
authors.initials: KS
authors.lastname: Furtado
authors.affiliation: Laboratory of Diet, Nutrition, and Cancer, Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Fábia
authors.initials: F
authors.lastname: de Oliveira Andrade
authors.affiliation: Laboratory of Diet, Nutrition, and Cancer, Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Campos
authors.affiliation: Laboratory of Nutrigenomics and Programming, Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Mariana Papaléo
authors.initials: MP
authors.lastname: Rosim
authors.affiliation: Laboratory of Diet, Nutrition, and Cancer, Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Vargas-Mendez
authors.affiliation: Laboratory of Diet, Nutrition, and Cancer, Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Henriques
authors.affiliation: Laboratory of Diet, Nutrition, and Cancer, Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: De Conti
authors.affiliation: Laboratory of Diet, Nutrition, and Cancer, Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Scolastici
authors.affiliation: Laboratory of Experimental Chemical Carcinogenesis, Department of Morphology, Botucatu, Institute of Biosciences, São Paulo State University, São Paulo, Brazil.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Barbisan
authors.affiliation: Laboratory of Striated Muscle Biology, Department of Morphology, Botucatu, Institute of Biosciences, São Paulo State University, São Paulo, Brazil.
authors.forename: Robson Francisco
authors.initials: RF
authors.lastname: Carvalho
authors.affiliation: Laboratory of Diet, Nutrition, and Cancer, Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Fernando Salvador
authors.initials: FS
authors.lastname: Moreno
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D045792:Norisoprenoids / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016588:Anticarcinogenic Agents; D035683:MicroRNAs; D045792:Norisoprenoids; C008157:beta-ionone
keywords: chemopreventive agent; hepatocarcinogenesis; miRNA; βI