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上皮-间质转化标志物PRRX1和miR-146b-5p在甲状腺乳头状癌进展中的作用

The roles of the epithelial-mesenchymal transition marker PRRX1 and miR-146b-5p in papillary thyroid carcinoma progression.

作者信息

Hardin Heather, Guo Zhenying, Shan Weihua, Montemayor-Garcia Celina, Asioli Sofia, Yu Xiao-Min, Harrison April D, Chen Herbert, Lloyd Ricardo V

机构信息

Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Department of Biomedical Sciences and Human Oncology, University of Turin, Turin, Italy.

出版信息

Am J Pathol. 2014 Aug;184(8):2342-54. doi: 10.1016/j.ajpath.2014.04.011. Epub 2014 Jun 17.

Abstract

Thyroid carcinoma is the most common endocrine malignancy, and papillary thyroid carcinoma represents the most common thyroid cancer. Papillary thyroid carcinomas that invade locally or metastasize are associated with a poor prognosis. We found that, during epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1), papillary thyroid carcinoma cells acquired increased cancer stem cell-like features and the transcription factor paired-related homeobox protein 1 (PRRX1; alias PRX-1), a newly identified EMT inducer, was markedly up-regulated. miR-146b-5p was also transiently up-regulated during EMT, and in siRNA experiments miR-146b-5p had an inhibitory role on cell proliferation and invasion during TGF-β1-induced EMT. We conclude that papillary thyroid carcinoma tumor cells exhibit increased cancer stem cell-like features during TGF-β1-induced EMT, that miR-146b-5p has a role in cell proliferation and invasion, and that PRRX1 plays an important role in papillary thyroid carcinoma EMT and disease progression.

摘要

甲状腺癌是最常见的内分泌恶性肿瘤,而乳头状甲状腺癌是最常见的甲状腺癌。局部侵袭或转移的乳头状甲状腺癌预后较差。我们发现,在转化生长因子-β1(TGF-β1)诱导的上皮-间质转化(EMT)过程中,乳头状甲状腺癌细胞获得了更多癌干细胞样特征,并且转录因子配对相关同源盒蛋白1(PRRX1;别名PRX-1),一种新发现的EMT诱导因子,显著上调。miR-146b-5p在EMT过程中也短暂上调,并且在小干扰RNA实验中,miR-146b-5p在TGF-β1诱导的EMT过程中对细胞增殖和侵袭具有抑制作用。我们得出结论,在TGF-β1诱导的EMT过程中,乳头状甲状腺癌肿瘤细胞表现出更多癌干细胞样特征,miR-146b-5p在细胞增殖和侵袭中发挥作用,并且PRRX1在乳头状甲状腺癌EMT和疾病进展中起重要作用。

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