USP7 promotes proliferation of papillary thyroid carcinoma cells through TBX3-mediated p57 KIP2 repression

Mol Cell Endocrinol. 2020 Dec 1;518:111037. doi: 10.1016/j.mce.2020.111037. Epub 2020 Sep 20.

Abstract

Ubiquitin-specific protease 7 (USP7/HAUSP) is known to regulate multiple cellular phenomena, including cell cycle progression and proliferation, and is involved in binding and stabilizing specific target proteins through deubiquitylation. However, the detailed role of USP7 in papillary thyroid carcinoma (PTC) remains to be investigated. In this study, our results showed that USP7 was upregulated in PTC tissues compared with adjacent nontumour tissues. Consistently, a series of gain/loss functional assays in vivo and in vitro demonstrated the role of USP7 in promoting PTC cell proliferation. Furthermore, we showed that there was a negative correlation between USP7 and the CDK inhibitor p57KIP2 expression in PTC tissues and that USP7 facilitated PTC cell proliferation by inhibiting p57KIP2. Mechanistically, USP7 inhibited p57KIP2 expression by modulating TBX3, directly binding to TBX3, and decreasing its ubiquitination and degradation. Our findings demonstrated that USP7 played a critical oncogenic role in PTC tumorigenesis, suggesting that USP7 might act as a prognostic and therapeutic target for PTC progression.

Keywords: Papillary thyroid carcinoma; Proliferation; TBX3; USP7; p57(KIP2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / genetics
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics*
  • Humans
  • RNA Interference
  • Signal Transduction / genetics
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / physiology*
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*
  • Ubiquitin-Specific Peptidase 7 / physiology*

Substances

  • Cyclin-Dependent Kinase Inhibitor p57
  • T-Box Domain Proteins
  • TBX3 protein, human
  • USP7 protein, human
  • Ubiquitin-Specific Peptidase 7