TRIM27 regulates the expression of PDCD4 by the ubiquitin‑proteasome pathway in ovarian and endometrial cancer cells

Oncol Rep. 2022 Jul;48(1):120. doi: 10.3892/or.2022.8331. Epub 2022 May 18.

Abstract

Programmed cell death 4 (PDCD4) is regarded as an important tumor suppressor that is lowly expressed or deleted in numerous human types of cancer, including ovarian and endometrial cancer. Tripartite motif‑containing 27 (TRIM27) is closely related to the occurrence and development of tumors and is highly expressed in numerous types of cancer such as ovarian and endometrial cancer. PDCD4 can be degraded through ubiquitination, while TRIM27 has the E3 ubiquitin ligase activity. However, whether TRIM27 may regulate the expression of PDCD4 by ubiquitination effect remains unclear. In the present study, the expression of PDCD4 and TRIM27 in different ovarian and endometrial cancer cell lines was detected by reverse transcription‑quantitative PCR (RT‑qPCR), western blotting and immunocytochemistry. The impact of TRIM27 overexpression and knockdown on PDCD4 expression and the effective mechanism of TRIM27 regulating PDCD4 expression were also investigated in vitro by RT‑qPCR, western blotting, co‑immunoprecipitation assay, Transwell migration and Matrigel invasion assays. The results showed that the expression of TRIM27 and PDCD4 had a negative association at the protein level, and the distribution of TRIM27 and PDCD4 proteins had a phenomenon of co‑localization in different ovarian and endometrial cancer cell lines. TRIM27 promoted the degradation of PDCD4 through the ubiquitin‑proteasome pathway. To sum up, TRIM27 could increase the migration and invasion of ovarian and endometrial cancer cells by promoting the ubiquitination and degradation of PDCD4. The present findings may provide a new target for the treatment of ovarian and endometrial cancer.

Keywords: ovarian and endometrial cancer; programmed cell death 4; tripartite motif‑containing 27; ubiquitin‑proteasome pathway.

MeSH terms

  • Apoptosis Regulatory Proteins* / genetics
  • Apoptosis Regulatory Proteins* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Endometrial Neoplasms* / genetics
  • Female
  • Humans
  • Nuclear Proteins* / metabolism
  • Proteasome Endopeptidase Complex* / genetics
  • Proteasome Endopeptidase Complex* / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Transcription Factors / metabolism
  • Ubiquitins

Substances

  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • PDCD4 protein, human
  • RNA-Binding Proteins
  • TRIM27 protein, human
  • Transcription Factors
  • Ubiquitins
  • Proteasome Endopeptidase Complex