Abstract
Constitutive photomorphogenic1 (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, etsvariant1 (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 ACHNcells 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 RCCACHNcells, and inhibit the migration and invasion of ACHNcells. In addition, ETV1 and matrix metalloproteinase7 (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 ACHNcells inhibited the migration and invasion of ACHNcells, and downregulated ETV1 and MMP7 expression levels. The present study demonstrated the tumor suppressive role of COP1 in RCC by inhibiting cell migration.
Highlights
Renal cell carcinoma (RCC) is a lethal urological cancer [1,2] and accounts for ~3% of all adult malignancies worldwide [3]
Reduced Constitutive photomorphogenic 1 (COP1) and upregulated ets variant 1 (ETV1) mRNA and protein expression levels in RCC tissue samples are associated with tumor malignancy
To investigate the role of COP1 and its downstream factor, ETV1 in RCC, the expression levels of the two markers were determined in 49 RCC specimens
Summary
Renal cell carcinoma (RCC) is a lethal urological cancer [1,2] and accounts for ~3% of all adult malignancies worldwide [3]. Due to the rareness of biomarkers in the early diagnosis of RCC, >20% of patients with RCC exhibit distant metastasis at their first diagnosis [4]. RCC is resistant to radiation therapy and chemotherapy, which are usually effective for other types of adult malignancy. Surgery is the first choice of treatment for the early or intermediate stage of RCC. ~30% of the patients undergoing nephrectomy for clinically localized RCC develop relapse at distant sites [5]. The 5‐year survival rate is 65‐90% in cases without cancer metastasis; this is reduced in cases where the cancer has metastasized [6]
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