MicroRNAs let7 expression in thyroid cancer: correlation with their deputed targets HMGA2 and SLC5A5
MicroRNAs let7 expression in thyroid cancer: correlation with their deputed targets HMGA2 and SLC5A5
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DOI：
10.1007/s00432-016-2138-z
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发表时间：
2016-06-01
影响因子：
3.6
通讯作者：
Di Fazio, Pietro
中科院分区：
文献类型：
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作者：
Damanakis, Alexander I.;Eckhardt, Sabine;Di Fazio, Pietro
甲状腺癌（TC）是最常见的内分泌恶性肿瘤，其发病率在全球范围内增加。microRNA已被证明在肿瘤中异常表达，并可能成为TC患者的有效诊断标志物。我们的目的是分析肿瘤抑制因子hsa-let 7 b-5 p和hsa-let 7 f-5 p及其预测的靶点SLC 5A 5（NIS）和HMGA 2在乳头状甲状腺癌（PTC）、滤泡状甲状腺癌（FTC）和间变性甲状腺癌（ATC）中的表达。分析8例FTC、14例PTC、12例ATC和3例正常甲状腺组织样本的pre-let 7 b表达，hsa-let 7 b-5 p和hsa-let 7 f-5 p作为SLC 5A 5和HMGA 2。FTC患者hsa-let 7 b-5 p及其前体蛋白表达明显下调。hsa-let 7 f-5 p过表达，SLC 5A 5被强烈抑制。HMGA 2过表达，反映与其调节let 7 miRNAs无关。PTC样品的特征在于hsa-let 7 b-5 p、其前体和hsa-let 7 f-5 p的上调。与正常甲状腺组织相比，SLC 5A 5被强烈抑制。如FTC所示，HMGA 2也过表达。ATC样品显示出与PTC相似的miRNA谱。与FTC和PTC相比，这些患者显示稳定或上调的SLC 5A 5和HMGA 2。HMGA 2的表达与调节let 7 miRNAs无关。有趣的是，SLC 5A 5在FTC和PTC中下调。hsa-let-7 f-5 p可调控其表达。ATC显示SLC 5A 5/hsa-let 7 f-5 p相关性丧失。ATC中的SLC 5A 5需要进一步研究以阐明改变其表达的遗传/表观遗传机制。
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.