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Reduced expression of THRβ in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression

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Abstract

Purpose

Down-regulation of thyroid hormone receptor beta (THRβ) gene has been described in several human malignancies, including thyroid cancer. In this study, we analyzed THRβ mRNA expression in surgical specimens from a series of human papillary thyroid carcinomas (PTCs), characterized by their genotypic and clinical–biological features.

Methods

Thirty-six PTCs were divided into two groups according to the 2009 American Thyroid Association risk classification (17 low, 19 intermediate), and each group was divided into subgroups based on the presence or absence of the BRAFV600E mutation (21 BRAF mutated, 15 BRAF wild type). Gene expression was analyzed using fluidic cards containing probes and primers specific for the THRβ gene, as well as for genes of thyroperoxidase (TPO), sodium/iodide symporter (NIS), thyroglobulin (Tg) and thyroid stimulating hormone receptor (TSH-R) and for some miRNAs involved in thyroid neoplasia and targeting THRβ. The mRNA levels of each tumor tissue were compared with their correspondent normal counterpart.

Results

THRβ transcript was down-regulated in all PTCs examined. No significant differences were found between intermediate- vs low-risk PTCs patients, and BRAF-mutated vs BRAF wild-type groups. THRβ expression was directly correlated with NIS, TPO, Tg and TSH-R, and inversely correlated to miR-21, -146a, -181a and -221 expression.

Conclusions

Our results demonstrate that down-regulation of THRβ is a common feature of PTCs. While it is not associated with a more aggressive phenotype of PTC, it correlates with the reduction of all the markers of differentiation and is associated with overexpression of some miRNAs supposed to play a role in thyroid tumorigenesis.

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Acknowledgments

This study was supported by the Fondazione Umberto Di Mario and by Banca d’Italia.

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

The authors declare that informed consent was obtained from all individual participants included in the study.

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Author notes

    Authors and Affiliations

    1. Department of Internal Medicine and Medical Specialties, University of Rome “Sapienza”, Viale del Policlinico155, 00161, Rome, Italy

      F. Rosignolo, M. Sponziello, A. Verrienti, M. Dima, V. Pecce & C. Durante

    2. Department of Health Sciences, University of Catanzaro ‘Magna Graecia’, 88100, Catanzaro, Italy

      V. Maggisano, M. Celano & M. D’Agostino

    3. Department of Radiological, Oncological and Pathological Sciences, University of Rome “Sapienza”, 00161, Rome, Italy

      C. R. T. Di Gioia

    4. Department of Surgical Sciences, University of Rome “Sapienza”, 00161, Rome, Italy

      L. Giacomelli

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    1. F. Rosignolo
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    2. V. Maggisano
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    4. M. Celano
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    Corresponding author

    Correspondence to C. Durante.

    Additional information

    F. Rosignolo and V. Maggisano equally contributed to this work.

    Electronic supplementary material

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    40618_2015_309_MOESM1_ESM.ppt

    Fig. S1 Correlation between miRNAs and thyroid-specific genes in human PTCs mRNA levels of TPO are significantly and inversely correlated to expression levels of miR-21 (a). mRNA levels of TG are significantly and inversely correlated to expression levels of miR-21 (b) and miR-146a (c). Correlations between miRNAs and thyroid-specific genes were analyzed by the Spearman rho rank correlation coefficient. Supplementary material 1 (PPT 248 kb)

    Supplementary material 2 (DOC 104 kb)

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    Rosignolo, F., Maggisano, V., Sponziello, M. et al. Reduced expression of THRβ in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression. J Endocrinol Invest 38, 1283–1289 (2015). https://doi.org/10.1007/s40618-015-0309-4

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    • DOI: https://doi.org/10.1007/s40618-015-0309-4

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