title: 2-Iodohexadecanal inhibits thyroid cell growth in part through the induction of let-7f microRNA.
abstract: It is well known that pituitary TSH exerts the major task in the regulation of thyroid function. However, this gland is capable of certain degree of autonomy, independently of TSH control. Iodine plays an important role in thyroid physiology and biochemistry. The thyroid is capable of producing different iodolipids such as 2-iodohexadecanal (2-IHDA). It was shown that this iodolipid mimic some of the inhibitory effects of excess iodide on several thyroid parameters.
  
  
  OBJECTIVE
  To identify the miRNAs regulated by 2-IHDA in rat thyroid cells and likely characterize their role in thyroid cell proliferation and function.
  
  
  RESULTS
  FRTL-5 cells were grown in the presence of TSH and treated with 2-IHDA. Among the miRNAs up-regulated by 2-IHDA we focused on miR-let-7f and miR-138. When we transfected the miRNAs, miR-let-7f but not miR-138 overexpression inhibited proliferation of FRTL 5 cells, while miR-let-7f inhibition restored cell growth in 2-IHDA treated cultures. Analysis of cell cycle by flow cytometric DNA analysis revealed that miR-let-7f inhibition reduced the percentage of 2-IHDA treated cells in G1 phase and an increased of the percentage of cells in S phase was observed upon anti-let-7f transfection. The expresion of Cyclin D1 and Cyclin D3 were reduced after the transfection of miR-let-7f and miR-138, respectively. In in vivo studies we observed that miR-let-7f and miR-138 were up regulated by 2-IHDA during goiter involution.
  
  
  CONCLUSIONS
  These results suggest that the inhibitory effects of 2-IHDA on FRTL-5 thyroid cell proliferation are mediated in part through the induction of let-7f microRNA.
authors.affiliation: Nuclear Biochemistry Division, Argentine National Atomic Energy Commission, Argentina.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Salvarredi
authors.affiliation: Nuclear Biochemistry Division, Argentine National Atomic Energy Commission, Argentina.
authors.forename: Lisa
authors.initials: L
authors.lastname: Thomasz
authors.affiliation: Nuclear Biochemistry Division, Argentine National Atomic Energy Commission, Argentina.
authors.forename: Luciano E
authors.initials: LE
authors.lastname: Rossich
authors.affiliation: I.R.I.B.H.M., Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Manuel
authors.initials: M
authors.lastname: Saiselet
authors.affiliation: Nuclear Biochemistry Division, Argentine National Atomic Energy Commission, Argentina; Department of Human Biochemistry, University of Buenos Aires School of Medicine, Buenos Aires, Argentina.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Pisarev
authors.affiliation: IEOS, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.affiliation: Nuclear Biochemistry Division, Argentine National Atomic Energy Commission, Argentina. Electronic address: juvenal@cnea.gov.ar.
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Juvenal
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects*; D013972:Thyrotropin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000447:Aldehydes; C581260:MIRN138 microRNA, rat; C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; C065952:2-iodohexadecanal; D013972:Thyrotropin
keywords: Iodine; Iodohexadecanal; Iodolipids; Thyroid; miR-138; miR-let-7f; miRNAs