COP1 is downregulated in renal cell carcinoma (RCC) and inhibits the migration of RCC ACHN cells in vitro

Mol Med Rep. 2016 Aug;14(2):1371-8. doi: 10.3892/mmr.2016.5373. Epub 2016 Jun 7.

Abstract

Constitutive photomorphogenic 1 (COP1) belongs to the COP‑de-etiolated (DET)‑fusca (FUS) protein family and has been demonstrated to suppress prostate adenocarcinomas and other types of tumor, such as liver and gastric cancer. The present study investigated the expression of COP1 and its downstream factor, ets variant 1 (ETV1) in renal cell carcinoma (RCC) tissue samples, and evaluated the correlation of COP1 expression levels with the clinicopathological characteristics of RCC. In addition, the role of COP1 in the proliferation and migration of RCC ACHN cells was investigated. The results demonstrated significantly downregulated COP1 expression levels in the RCC intratumors, which was negatively associated with clinicopathological characteristics, such as tumor size, tumor‑node‑metastasis (TNM) stage and lymph node or distant metastasis. COP1 was demonstrated to markedly reduce the colony size of RCC ACHN cells, and inhibit the migration and invasion of ACHN cells. In addition, ETV1 and matrix metalloproteinase 7 (MMP7) mRNA and protein expression levels were significantly downregulated by the overexpressed COP1. Thus, the results of the present study demonstrate the reduced expression of COP1 and the upregulated expression of ETV1 in RCC tissue samples, which was associated with a high tumor-node-metastasis stage of RCC. Furthermore, the overexpression of COP1 in the RCC ACHN cells inhibited the migration and invasion of ACHN cells, and downregulated ETV1 and MMP7 expression levels. The present study demonstrated the tumor suppressive role of COP1 in RCC by inhibiting cell migration.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 7 / metabolism
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Proteolysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Burden
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • DNA-Binding Proteins
  • ETV1 protein, human
  • RNA, Messenger
  • Transcription Factors
  • COP1 protein, human
  • Ubiquitin-Protein Ligases
  • Matrix Metalloproteinase 7