Reduced expression of THRβ in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression
Reduced expression of THRβ in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression
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DOI：
10.1007/s40618-015-0309-4
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发表时间：
2015-12-01
影响因子：
5.4
通讯作者：
Durante, C.
中科院分区：
文献类型：
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作者：
Rosignolo, F.;Maggisano, V.;Durante, C.
目的甲状腺激素受体β（THR β）基因在包括甲状腺癌在内的多种人类恶性肿瘤中表达下调。本研究分析了一系列人甲状腺乳头状癌（PTC）手术标本中THR β mRNA的表达，并根据其基因型和临床生物学特征进行了分析。（17个低，19个中等），并且基于BRAFV 600 E突变的存在或不存在将每组分成亚组（21个BRAF突变，15个BRAF野生型）。使用含有THR β基因特异性探针和引物的流体卡分析基因表达，以及甲状腺过氧化物酶（TPO）、钠/碘同向转运体（NIS）、甲状腺球蛋白（Tg）和促甲状腺激素受体（TSH-R）的基因，以及参与甲状腺瘤形成和靶向THR β的一些miRNA。结果THR β mRNA在所有肿瘤组织中均表达下调。在中危与低危PTC患者之间，以及BRAF突变与BRAF野生型组之间没有发现显著差异。THR β表达与NIS、TPO、Tg和TSH-R呈正相关，与miR-21、-146 a、-181 a和-221呈负相关。虽然它与PTC更具侵袭性的表型无关，但它与所有分化标志物的减少相关，并与一些在甲状腺肿瘤发生中发挥作用的miRNA的过表达相关。
Purpose Down-regulation of thyroid hormone receptor beta (THR beta) gene has been described in several human malignancies, including thyroid cancer. In this study, we analyzed THR beta 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 THR beta 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 THR beta. The mRNA levels of each tumor tissue were compared with their correspondent normal counterpart.Results THR beta 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. THR beta 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 THR beta 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.