Regular article
Tumorigenesis and neoplastic progression
The Roles of the Epithelial-Mesenchymal Transition Marker PRRX1 and miR-146b-5p in Papillary Thyroid Carcinoma Progression

https://doi.org/10.1016/j.ajpath.2014.04.011Get rights and content
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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.

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Supported by NIH grant R01-CA121115 (H.C.) and American Cancer Society MEN2 Thyroid Cancer Professorship (H.C.), by start-up funding from the Department of Pathology (R.V.L.), and by NIH Cancer Center Support Grant P30-CA014520-39 to the University of Wisconsin Carbone Cancer Center.

Disclosures: None declared.