Damanakis Alexander I, Eckhardt Sabine, Wunderlich Annette, Roth Silvia, Wissniowski Thaddeus T, Bartsch Detlef K, Di Fazio Pietro
Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany.
Division of Gastroenterology and Endocrinology, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany.
J Cancer Res Clin Oncol. 2016 Jun;142(6):1213-20. doi: 10.1007/s00432-016-2138-z. Epub 2016 Mar 9.
Thyroid cancer (TC), the most common endocrine malignancy, increases its incidence worldwide. MicroRNAs have been shown to be abnormally expressed in tumors and could represent valid diagnostic markers for patients affected by TC. Our aim was to analyze the expression of tumorsuppressor hsa-let7b-5p and hsa-let7f-5p, together with their predicted targets SLC5A5 (NIS) and HMGA2, in papillary (PTC), follicular (FTC) and anaplastic (ATC).
8 FTC, 14 PTC, 12 ATC and three normal thyroid tissue samples were analyzed for the expression of pre-let7b, hsa-let7b-5p and hsa-let7f-5p as SLC5A5 and HMGA2 by RT-qPCR. Data were analyzed by REST 2008.
FTC patients showed a significant down-regulation of hsa-let7b-5p and its precursor. hsa-let7f-5p was overexpressed, and SLC5A5 was strongly suppressed. HMGA2 was overexpressed, reflecting no correlation with its regulatory let7 miRNAs. PTC samples were characterized by up-regulation of hsa-let7b-5p, its precursor and hsa-let7f-5p. SLC5A5 was strongly suppressed in comparison with normal thyroid tissue. HMGA2 was overexpressed, as shown in FTC, also. ATC samples showed a similar miRNAs profile as PTC. In contrast with FTC and PTC, these patients showed a stable or up-regulated SLC5A5 and HMGA2.
Expression of HMGA2 is not correlated with the regulatory let7 miRNAs. Interestingly, SLC5A5 was down-regulated in FTC and PTC. Its expression could be modulated by hsa-let-7f-5p. ATC showed a loss of SLC5A5/hsa-let7f-5p correlation. SLC5A5, in ATC, needs further investigation to clarify the genetic/epigenetic mechanism altering its expression.
甲状腺癌（TC）是最常见的内分泌恶性肿瘤，其在全球的发病率呈上升趋势。微小RNA已被证明在肿瘤中异常表达，可能是TC患者有效的诊断标志物。我们的目的是分析抑癌基因hsa-let7b-5p和hsa-let7f-5p及其预测靶点SLC5A5（钠碘同向转运体，NIS）和HMGA2在乳头状癌（PTC）、滤泡状癌（FTC）和未分化癌（ATC）中的表达情况。
采用逆转录定量聚合酶链反应（RT-qPCR）分析8例FTC、14例PTC、12例ATC及3例正常甲状腺组织样本中pre-let7b、hsa-let7b-5p、hsa-let7f-5p以及SLC5A5和HMGA2的表达。数据采用REST 2008软件进行分析。
FTC患者中hsa-let7b-5p及其前体显著下调。hsa-let7f-5p过表达，SLC5A5受到强烈抑制。HMGA2过表达，表明其与调控它的let7微小RNA无相关性。PTC样本的特征是hsa-let7b-5p及其前体和hsa-let7f-5p上调。与正常甲状腺组织相比，SLC5A5受到强烈抑制。HMGA2也过表达，与FTC情况相同。ATC样本显示出与PTC相似的微小RNA表达谱。与FTC和PTC不同，这些患者的SLC5A5和HMGA2表达稳定或上调。
HMGA2的表达与调控它的let7微小RNA无相关性。有趣的是，SLC5A5在FTC和PTC中下调。其表达可能受hsa-let-7f-5p调控。ATC中SLC5A5/hsa-let7f-5p的相关性消失。ATC中SLC5A5表达改变的遗传/表观遗传机制需要进一步研究以阐明。
