Expression and clinicopathological role of miR146a in thyroid follicular carcinoma
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ORIGINAL ARTICLE
Expression and clinicopathological role of miR146a in thyroid follicular carcinoma 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 Simoni1,2,4 Giulia Brigante1,4 ●
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Received: 31 May 2018 / Accepted: 14 January 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
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 receptorassociated 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. Keywords Follicular thyroid carcinoma miR146a IRAK1 TRAF6 ●
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Introduction
Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-019-01845-9) contains supplementary material, which is available to authorised users.
More than 95% of thyroid carcinomas derive from follicular thyroid cells and are classified into well-differentiated papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC; conventional or oncocytic type) [1]. FTC is the second most common thyroid carcinoma after PTC and its incidence peak is between the ages of 40 and 60
* Manuela Simoni manuela.si
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