Increased expression of PSME2 is associated with clear cell renal cell carcinoma invasion by regulating BNIP3‑mediated autophagy

Int J Oncol. 2021 Dec;59(6):106. doi: 10.3892/ijo.2021.5286. Epub 2021 Nov 15.

Abstract

Previous studies have showed that proteasome activator complex subunit 2 (PSME2) may play a role in some types of cancer. However, the involvement of PSME2 in clear cell renal cell carcinoma (ccRCC) remains unknown. The aim of the present study was to assess the poorly understood function of PSME2 expression in renal carcinoma. Using bioinformatics analysis, PSME2 mRNA expression profiles were investigated, along with its potential prognostic value and its functional enrichment. Signaling pathways and putative hub genes associated with PSME2 in ccRCC were identified. Based on the bioinformatics analysis results, immunohistochemistry of human ccRCC samples and renal carcinoma cell lines (CAKI‑1 and 786‑O) transfected with short interfering RNA targeting PSME2 were analyzed using western blot analysis, reverse transcription‑quantitative PCR, immunofluorescence, and Cell Counting Kit‑8, Transwell and transmission electron microscope assays. The results showed that when PSME2 expression was knocked down, the invasive abilities of the tumor cell lines were reduced, while autophagy was enhanced. The present study demonstrated that PSME2 was associated with the invasion ability of ccRCC cell lines by inhibiting BNIP3‑mediated autophagy. In summary, PSME2 could be used as a prognostic factor and a promising therapeutic target in ccRCC.

Keywords: BCL2 interacting protein; autophagy; clear cell renal cell carcinoma; invasion; proteasome activator complex subunit 2.

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Autophagy*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Proliferation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • BNIP3 protein, human
  • Biomarkers, Tumor
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • PSME2 protein, human
  • Proteasome Endopeptidase Complex

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (grant no. 21772131) and the Fundamental Research Funds for the Science and Technology Department of Sichuan Province (grant nos. 2019YFSY0004 and 2019YFS0298).