CSN5 Promotes Carcinogenesis of Thyroid Carcinoma Cells Through ANGPTL2

Endocrinology. 2021 Mar 1;162(3):bqaa206. doi: 10.1210/endocr/bqaa206.

Abstract

COP9 signalosome subunit 5 (CSN5) plays a key role in carcinogenesis of multiple cancers and contributes to the stabilization of target proteins through deubiquitylation. However, the underlying role of CSN5 in thyroid carcinoma has not been reported. In this research, our data showed that CSN5 was overexpressed in thyroid carcinoma tissues compared with paracancerous tissues. Furthermore, a series of gain/loss functional assays were performed to demonstrate the role of CSN5 in facilitating thyroid carcinoma cell proliferation and metastasis. Additionally, we found there was a positive correlation between CSN5 and angiopoietin-like protein 2 (ANGPTL2) protein levels in thyroid carcinoma tissues and that CSN5 promoted thyroid carcinoma cell proliferation and metastasis through ANGPTL2. We also identified the underlying mechanism that CSN5 elevated ANGPTL2 protein level by directly binding it, decreasing its ubiquitination and degradation. Overall, our results highlight the significance of CSN5 in promoting thyroid carcinoma carcinogenesis and implicate CSN5 as a promising candidate for thyroid carcinoma treatment.

Keywords: ANGPTL2; CSN5; invasion; migration; proliferation; thyroid carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-Like Protein 2
  • Angiopoietin-like Proteins / metabolism
  • Angiopoietin-like Proteins / physiology*
  • Animals
  • COP9 Signalosome Complex / physiology*
  • Carcinogenesis / genetics*
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Peptide Hydrolases / physiology*
  • Protein Processing, Post-Translational / genetics
  • Proteolysis
  • Signal Transduction / genetics
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology
  • Ubiquitination / genetics

Substances

  • ANGPTL2 protein, human
  • Angiopoietin-Like Protein 2
  • Angiopoietin-like Proteins
  • Intracellular Signaling Peptides and Proteins
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex