SDC4 Gene Silencing Favors Human Papillary Thyroid Carcinoma Cell Apoptosis and Inhibits Epithelial Mesenchymal Transition via Wnt/β-Catenin Pathway

Mol Cells. 2018 Sep 30;41(9):853-867. doi: 10.14348/molcells.2018.0103. Epub 2018 Aug 31.

Abstract

As the most common type of endocrine malignancy, papillary thyroid cancer (PTC) accounts for 85-90% of all thyroid cancers. In this study, we presented the hypothesis that SDC4 gene silencing could effectively attenuate epithelial mesenchymal transition (EMT), and promote cell apoptosis via the Wnt/β-catenin signaling pathway in human PTC cells. Bioinformatics methods were employed to screen the determined differential expression levels of SDC4 in PTC and adjacent normal samples. PTC tissues and adjacent normal tissues were prepared and their respective levels of SDC4 protein positive expression, in addition to the mRNA and protein levels of SDC4, Wnt/β-catenin signaling pathway, EMT and apoptosis related genes were all detected accordingly. Flow cytometry was applied in order to detect cell cycle entry and apoptosis. Finally, analyses of PTC migration and invasion abilities were assessed by using a Transwell assay and scratch test. In PTC tissues, activated Wnt/β-catenin signaling pathway, increased EMT and repressed cell apoptosis were determined. Moreover, the PTC K1 and TPC-1 cell lines exhibiting the highest SDC4 expression were selected for further experiments. In vitro experiments revealed that SDC4 gene silencing could suppress cell migration, invasion and EMT, while acting to promote the apoptosis of PTC cells by inhibiting the activation of the Wnt/β-catenin signaling pathway. Besides, si-β-catenin was observed to inhibit the promotion of PTC cell migration and invasion caused by SDC4 overexpression. Our study revealed that SDC4 gene silencing represses EMT, and enhances cell apoptosis by suppressing the activation of the Wnt/β-catenin signaling pathway in human PTC.

Keywords: Papillary thyroid carcinoma; SDC4; Wnt/β-catenin signaling pathway; epithelial mesenchymal transition.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Silencing
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Syndecan-4 / genetics
  • Syndecan-4 / metabolism*
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*
  • Wnt Signaling Pathway / genetics*

Substances

  • SDC4 protein, human
  • Syndecan-4