title: miRNA expression in anaplastic thyroid carcinomas.
abstract: Anaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid neoplasia and represents an end stage of thyroid tumor progression. No effective treatment exists so far. In this study, we analyzed the miRNA expression profiles of 11 ATC by microarrays and their relationship with the mRNA expression profiles of the same 11 ATC samples. ATC show distinct miRNA expression profiles compared to other less aggressive thyroid tumor types. ATC show 18 commonly deregulated miRNA compared to normal thyroid tissue (17 downregulated and 1 upregulated miRNA). First, the analysis of a combined approach of the mRNA gene expression and of the bioinformatically predicted mRNA targets of the deregulated miRNA suggested a role for these regulations in the epithelial to mesenchymal transition (EMT) process in ATC. Second, the direct interaction between one of the upregulated mRNA target, the LOX gene which is an EMT key player, and a downregulated miRNA, the miR-29a, was experimentally validated by a luciferase assay in HEK cell. Third, we confirmed that the ATC tissue is composed of about 50% of tumor associated macrophages (TAM) and suggested, by taking into account our data and published data, their most likely direct or paracrine intercommunication between them and the thyroid tumor cells, amplifying the tumor aggressiveness. Finally, we demonstrated by in situ hybridization a specific thyrocyte localization of 3 of the deregulated miRNA: let-7g, miR-29a and miR-30e and we pointed out the importance of identifying the cell type localization before drawing any conclusion on the physiopathological role of a given gene.
authors.affiliation: Institute of Interdisciplinary Research (IRIBHM), School of Medicine, Université libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Aline
authors.initials: A
authors.lastname: Hébrant
authors.affiliation: Institute of Interdisciplinary Research (IRIBHM), School of Medicine, Université libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Floor
authors.affiliation: Institute of Interdisciplinary Research (IRIBHM), School of Medicine, Université libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Manuel
authors.initials: M
authors.lastname: Saiselet
authors.affiliation: Institute of Interdisciplinary Research (IRIBHM), School of Medicine, Université libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Aline
authors.initials: A
authors.lastname: Antoniou
authors.affiliation: Institute of Interdisciplinary Research (IRIBHM), School of Medicine, Université libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Alice
authors.initials: A
authors.lastname: Desbuleux
authors.affiliation: Institute of Interdisciplinary Research (IRIBHM), School of Medicine, Université libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Snyers
authors.affiliation: Institute of Interdisciplinary Research (IRIBHM), School of Medicine, Université libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: La
authors.affiliation: Institut Jules Bordet, Bruxelles, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Saint Aubain
authors.affiliation: Université de Lille 2, Faculté de Médecine, Lille, France; CHRU de Lille, Institut de Pathologie, Lille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
authors.affiliation: Institut Jules Bordet, Bruxelles, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Andry
authors.affiliation: Institute of Interdisciplinary Research (IRIBHM), School of Medicine, Université libre de Bruxelles, Campus Erasme, Brussels, Belgium; WELBIO, School of Medicine, Université libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Carine
authors.initials: C
authors.lastname: Maenhaut
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D065646:Thyroid Carcinoma, Anaplastic / Q000235:genetics*; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger