Elisa Pignatti1,2, Eleonora Vighi3, Elisa Magnani1, Elda Kara1, Luca Roncati4, Antonino Maiorana4,5, Daniele Santi1,4, Bruno Madeo4, Katia Cioni4, Cesare Carani1, Vincenzo Rochira1,4, Manuela Simoni6,7,8, Giulia Brigante1,4. 1. Department of Biomedical, Metabolic and Neural Sciences, Unit of Endocrinology, University of Modena and Reggio Emilia, Modena, Italy. 2. Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy. 3. Department of Life Science, University of Modena and Reggio Emilia, Modena, Italy. 4. Azienda Ospedaliero-Universitaria of Modena, Modena, Italy. 5. Department of Diagnostic and Clinical Medicine, and Public Health, University of Modena and Reggio Emilia, Modena, Italy. 6. Department of Biomedical, Metabolic and Neural Sciences, Unit of Endocrinology, University of Modena and Reggio Emilia, Modena, Italy. manuela.simoni@unimore.it. 7. Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy. manuela.simoni@unimore.it. 8. Azienda Ospedaliero-Universitaria of Modena, Modena, Italy. manuela.simoni@unimore.it.
Abstract
PURPOSE: Dysregulation of microRNA expression has been involved in the development and progression of follicular thyroid carcinoma (FTC). The aim of this work was to study the expression of miRNA146a in FTC and the association with clinicopathological features of the disease. METHODS: Thirty-eight patients affected by FTC were included in the study. Twenty patients carrying follicular thyroid adenoma (FA) were also enroled as the benign counterpart of FTC. Total RNA including miRNA146a was extracted from formalin-fixed paraffin-embedded (FFPE) pairs of affected/unaffected tissue and its expression was assessed by real-time PCR. Two selected target genes, TRAF6 (tumour necrosis factor receptor-associated factor 6) and IRAK1 (Il-1 receptor-associated kinase 1/2), were also analysed. RESULTS: miR146a expression in FTC tissue was overall not downregulated in malignant versus unaffected tissue, but its expression was inversely correlated with clinicopathological features of FTCs at diagnosis. A decreased expression of miR146a became apparent in FTC thyroid tissue of widely compared to minimally invasive tumours. However, miR146a expression differences between contralateral unaffected tissue (extra-FTC) and FTC were not observed regardless of clinicopathological features. IRAK1, a known target for miR146a, was upregulated in FTC and the increase was mainly appreciable in Hurtle FTC variant. Unexpectedly, miR146a did not correlate with TRAF6 showing an inverse trend compared to IRAK1 although both genes regulate the activity of nuclear factor- kB (NF-kB). CONCLUSION: The results of this study indicate that downregulation of miR146a, inversely correlated with clinicopathological features of FTCs at diagnosis and suggest a possible involvement of miR146a in FTC development. IRAK1 over-expression in FTC may be related to tumour development/progression. In vitro experiments are needed to support this hypothesis.
PURPOSE: Dysregulation of microRNA expression has been involved in the development and progression of follicular thyroid carcinoma (FTC). The aim of this work was to study the expression of miRNA146a in FTC and the association with clinicopathological features of the disease. METHODS: Thirty-eight patients affected by FTC were included in the study. Twenty patients carrying follicular thyroid adenoma (FA) were also enroled as the benign counterpart of FTC. Total RNA including miRNA146a was extracted from formalin-fixed paraffin-embedded (FFPE) pairs of affected/unaffected tissue and its expression was assessed by real-time PCR. Two selected target genes, TRAF6 (tumour necrosis factor receptor-associated factor 6) and IRAK1 (Il-1 receptor-associated kinase 1/2), were also analysed. RESULTS:miR146a expression in FTC tissue was overall not downregulated in malignant versus unaffected tissue, but its expression was inversely correlated with clinicopathological features of FTCs at diagnosis. A decreased expression of miR146a became apparent in FTC thyroid tissue of widely compared to minimally invasive tumours. However, miR146a expression differences between contralateral unaffected tissue (extra-FTC) and FTC were not observed regardless of clinicopathological features. IRAK1, a known target for miR146a, was upregulated in FTC and the increase was mainly appreciable in Hurtle FTC variant. Unexpectedly, miR146a did not correlate with TRAF6 showing an inverse trend compared to IRAK1 although both genes regulate the activity of nuclear factor- kB (NF-kB). CONCLUSION: The results of this study indicate that downregulation of miR146a, inversely correlated with clinicopathological features of FTCs at diagnosis and suggest a possible involvement of miR146a in FTC development. IRAK1 over-expression in FTC may be related to tumour development/progression. In vitro experiments are needed to support this hypothesis.
Authors: Azra Krek; Dominic Grün; Matthew N Poy; Rachel Wolf; Lauren Rosenberg; Eric J Epstein; Philip MacMenamin; Isabelle da Piedade; Kristin C Gunsalus; Markus Stoffel; Nikolaus Rajewsky Journal: Nat Genet Date: 2005-04-03 Impact factor: 38.330
Authors: Frank Weber; Rosemary E Teresi; Christoph E Broelsch; Andrea Frilling; Charis Eng Journal: J Clin Endocrinol Metab Date: 2006-07-05 Impact factor: 5.958
Authors: M Maragkakis; M Reczko; V A Simossis; P Alexiou; G L Papadopoulos; T Dalamagas; G Giannopoulos; G Goumas; E Koukis; K Kourtis; T Vergoulis; N Koziris; T Sellis; P Tsanakas; A G Hatzigeorgiou Journal: Nucleic Acids Res Date: 2009-04-30 Impact factor: 16.971