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

J Endocrinol Invest. 2015 Dec;38(12):1283-9. doi: 10.1007/s40618-015-0309-4. Epub 2015 May 24.

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.

Keywords: BRAF; Papillary thyroid carcinoma; Thyroid hormone receptor; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma, Papillary
  • Down-Regulation
  • Female
  • Gene Expression*
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Proto-Oncogene Proteins B-raf / genetics*
  • RNA, Messenger / metabolism
  • Thyroid Cancer, Papillary
  • Thyroid Hormone Receptors beta / genetics
  • Thyroid Hormone Receptors beta / metabolism*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Messenger
  • Thyroid Hormone Receptors beta
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf