USP20 regulates the stability of EMT transcription factor SOX4 and influences colorectal cancer metastasis

Pathol Res Pract. 2022 May:233:153879. doi: 10.1016/j.prp.2022.153879. Epub 2022 Apr 4.

Abstract

Background: Colorectal cancer (CRC) is a familiar malignancy accompanied by higher morbidity and mortality. The deubiquitination enzyme USP20 has been discovered to be one key factor in several cancers progression. SOX4 is a critical transcription factor to regulate the expression of various genes, and participates into the occurrence and progression of cancers. In this study, it was aimed to illustrate the role of USP20 and the regulatory relationship between USP20 and SOX4 in CRC.

Methods: The protein expressions of USP20, SOX4, E-cadherin, N-cadherin, Snail and slug were tested through western blot. The cell proliferation ability was verified through CCK-8 assay. The migration and invasion abilities were detected through Transwell assay. The mRNA expression of SOX4 was confirmed through RT-qPCR. The interaction between USP20 and SOX4 was notarized through Co-IP assay.

Result: Our study demonstrated that USP20 displayed higher expression, and facilitated CRC progression through regulating cell proliferation, migration, invasion and EMT process markers. USP20 was found to modulate SOX4 protein expression. Next, it was verified that USP20 regulated SOX4 degradation through deubiquitination. Finally, through rescue assays, we revealed that USP20 mediated SOX4 expression to accelerate CRC progression.

Conclusions: In this study, USP20 regulated the stability of EMT transcription factor SOX4 and aggravated colorectal cancer metastasis. This finding might highlight the function of USP20 in the treatment of CRC.

Keywords: CRC; EMT process; SOX4; USP20.

MeSH terms

  • Blotting, Western
  • Cell Proliferation
  • Colorectal Neoplasms* / genetics
  • Gene Expression Regulation
  • Humans
  • SOXC Transcription Factors / genetics
  • Transcription Factors*
  • Ubiquitin Thiolesterase

Substances

  • SOX4 protein, human
  • SOXC Transcription Factors
  • Transcription Factors
  • USP20 protein, human
  • Ubiquitin Thiolesterase