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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma / pathology*
  • Carcinoma, Papillary
  • Cell Line, Tumor
  • Disease Progression
  • Epithelial-Mesenchymal Transition / physiology*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Heterografts
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Mice
  • MicroRNAs / metabolism*
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / pathology*
  • Tissue Array Analysis
  • Transfection
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • Homeodomain Proteins
  • MIRN146 microRNA, human
  • MicroRNAs
  • PRRX1 protein, human
  • RNA, Small Interfering
  • Transforming Growth Factor beta1