title: Resveratrol and EGCG bind directly and distinctively to miR-33a and miR-122 and modulate divergently their levels in hepatic cells.
abstract: Modulation of miR-33 and miR-122 has been proposed to be a promising strategy to treat dyslipidemia and insulin resistance associated with obesity and metabolic syndrome. Interestingly, specific polyphenols reduce the levels of these mi(cro)RNAs. The aim of this study was to elucidate the effect of polyphenols of different chemical structure on miR-33a and miR-122 expression and to determine whether direct binding of the polyphenol to the mature microRNAs (miRNAs) is a plausible mechanism of modulation. The effect of two grape proanthocyanidin extracts, their fractions and pure polyphenol compounds on miRNA expression was evaluated using hepatic cell lines. Results demonstrated that the effect on miRNA expression depended on the polyphenol chemical structure. Moreover, miR-33a was repressed independently of its host-gene SREBP2. Therefore, the ability of resveratrol and epigallocatechin gallate to bind miR-33a and miR-122 was measured using (1)H NMR spectroscopy. Both compounds bound miR-33a and miR-122 and differently. Interestingly, the nature of the binding of these compounds to the miRNAs was consistent with their effects on cell miRNA levels. Therefore, the specific and direct binding of polyphenols to miRNAs emerges as a new posttranscriptional mechanism by which polyphenols could modulate metabolism.
authors.affiliation: Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, 43007, Spain and Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, 08034, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Baselga-Escudero
authors.forename: Cinta
authors.initials: C
authors.lastname: Blade
authors.forename: Aleix
authors.initials: A
authors.lastname: Ribas-Latre
authors.forename: Ester
authors.initials: E
authors.lastname: Casanova
authors.forename: Manuel
authors.initials: M
authors.lastname: Suárez
authors.forename: Josep Lluís
authors.initials: JL
authors.lastname: Torres
authors.forename: M Josepa
authors.initials: MJ
authors.lastname: Salvadó
authors.forename: Lluis
authors.initials: L
authors.lastname: Arola
authors.forename: Anna
authors.initials: A
authors.lastname: Arola-Arnal
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D064429:Fatty Acid Synthases / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D035683:MicroRNAs / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D000077185:Resveratrol; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D027843:Vitis / Q000737:chemistry
chemical_list: D064286:ATP Binding Cassette Transporter 1; D005419:Flavonoids; C531907:MIRN122 microRNA, human; C580643:MIRN122 microRNA, rat; C580642:MIRN33 microRNA, rat; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D010936:Plant Extracts; D059808:Polyphenols; D051782:Sterol Regulatory Element Binding Protein 2; D013267:Stilbenes; D002392:Catechin; C045651:epigallocatechin gallate; D064429:Fatty Acid Synthases; D000077185:Resveratrol