Abstract
PurposeTo study the detailed mechanisms of tumorigenesis and clinical outcomes of centrosomal protein 55 (CEP55) overexpression in renal cell carcinoma.Materials and methodsMicroarray analysis was performed to explore differentially expressed genes in five pairs of RCC tissues. Data of CEP55 expression and corresponding clinical information for 532 RCC patients of TCGA database were downloaded from cBioPortal. The expression of CEP55 in RCC tissues and cells was determined by real-time quantitative reverse transcription PCR (qRT-PCR), Western blot analysis and immunohistochemistry (IHC). Cells were transfected with siRNAs or lentivirus to regulate the expression of CEP55. The effects of CEP55 on proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT) of RCC cells were determined by MTS, migration and invasion assay and Western blot analysis.ResultsCEP55, one of the most upregulated genes in microarray analysis, was overexpressed in RCC tissues and cells. CEP55 expression was significantly correlated with poor outcome including neoplasm disease stage, histologic grade and TNM status, as well as survival status of patients. In vitro experiments showed that downregulation of CEP55 could dramatically inhibit RCC cell proliferation, migration and invasion, while overexpression of CEP55 could promote these biological behaviors. We further demonstrated that CEP55 knockdown suppressed epithelial–mesenchymal transition (EMT), which was mediated via upregulation of E-cadherin and downregulation of N-cadherin and ZEB1, through PI3K/AKT/mTOR pathway. In contrast, overexpression of CEP55 could promote EMT in RCC cells via the activation of PI3K/AKT/mTOR pathway. Importantly, inhibition of PI3K/AKT/mTOR pathway reduced the effects of CEP55 on the migration, invasion and EMT of RCC cells.ConclusionOur study showed that CEP55 could promote EMT through PI3K/AKT/mTOR pathway and might be an effective prognostic marker in RCC.
Highlights
Renal cell carcinoma (RCC) is a malignant cancer of the tubular cells of the kidney, which accounts for 2–3% of adult malignant tumors and its morbidity and mortality are still increasing [1]
We found that centrosomal protein 55 (CEP55) was overexpressed in RCC cells compared with HK-2 cells (Fig. 1c), which suggested that the abnormal expression level of CEP55 might be correlated with malignancy
We investigated the expression level of CEP55 in RCC tissues and adjacent normal tissues, and a panel of RCC cell lines
Summary
Renal cell carcinoma (RCC) is a malignant cancer of the tubular cells of the kidney, which accounts for 2–3% of adult malignant tumors and its morbidity and mortality are still increasing [1]. There is no effective treatment for metastatic renal cell carcinoma. Interferon-α (INF-α) and interleukin-2 (IL2), which were the standard for the treatment of metastatic RCC, fail to provide satisfactory clinical benefit because of their known significant toxicity and modest overall response rates (ORRs) [3]. Molecular-targeted therapy is one of the major strategies for the treatment of metastatic RCC. Several molecular-targeted therapies such as the mTOR inhibitor temsirolimus and the VEGF inhibitor bevacizumab have been proved to improve the clinical outcomes of RCC patients [4, 5]. Several breakthroughs have been achieved in the study of RCC, the underlying mechanisms of metastasis in renal cell carcinoma remain unclear.
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