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CDCA2 acts as an oncogene and induces proliferation of clear cell renal cell carcinoma cells.

ABSTRACT: Cell division cycle-associated 2 (CDCA2) plays an important role in regulating chromosome structure during mitosis. It is highly expressed in oral squamous cell carcinoma, neuroblastoma and lung adenocarcinoma, and its upregulation is positively associated with tumor progression. However, the expression, biological function and underlying mechanisms of the role of CDCA2 in clear cell renal cell carcinoma (ccRCC) remain poorly understood. In the present study, CDCA2 was demonstrated to be upregulated in ccRCC tissues compared with normal kidney tissue, where higher expression was generally associated with the degree of malignancy. Small interfering RNA-mediated knockdown of CDCA2 expression inhibited the viability and proliferation of 786-O and CAKI-1 cells, as measured by an MTT assay, colony formation assay and flow cytometry. Furthermore, western blot analysis suggested that CDCA2 regulates cell proliferation through the cell cycle-associated proteins cyclin D1 and cyclin dependent kinase 4, and the apoptotic protein Bcl-2. In conclusion, the present study indicated that CDCA2 may be an important factor in ccRCC progression and could be a potential therapeutic target in this disease.

SUBMITTER: Li F

PROVIDER: S-EPMC7039090 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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CDCA2 acts as an oncogene and induces proliferation of clear cell renal cell carcinoma cells.

Li Fang F Zhang Huahua H Li Qian Q Wu Fei F Wang Yu Y Wang Zhenzhen Z Wang Xiaofei X Huang Chen C

Oncology letters 20200121 3

Cell division cycle-associated 2 (CDCA2) plays an important role in regulating chromosome structure during mitosis. It is highly expressed in oral squamous cell carcinoma, neuroblastoma and lung adenocarcinoma, and its upregulation is positively associated with tumor progression. However, the expression, biological function and underlying mechanisms of the role of CDCA2 in clear cell renal cell carcinoma (ccRCC) remain poorly understood. In the present study, CDCA2 was demonstrated to be upregul ...[more]

PMID: 32194746

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Project description:BackgroundClear cell renal cell carcinoma (ccRCC) accounts for 60-70% of renal cell carcinoma (RCC) cases. Finding more therapeutic targets for advanced ccRCC is an urgent mission. The minichromosome maintenance proteins 2-7 (MCM2-7) protein forms a stable heterohexamer and plays an important role in DNA replication in eukaryotic cells. In the study, we provide a comprehensive study of MCM2-7 genes expression and their potential roles in ccRCC.MethodsThe expression and prognosis of the MCM2-7 genes in ccRCC were analyzed using data from TCGA, GEO and ArrayExpress. MCM2-7 related genes were identified by weighted co-expression network analysis (WGCNA) and Metascape. CancerSEA and GSEA were used to analyze the function of MCM2-7 genes in ccRCC. The gene effect scores (CERES) of MCM2-7, which reflects carcinogenic or tumor suppressor, were obtained from DepMap. We used clinical and expression data of MCM2-7 from the TCGA dataset and the LASSO Cox regression analysis to develop a risk score to predict survival of patients with ccRCC. The correlations between risk score and other clinical indicators such as gender, age and stage were also analyzed. Further validation of this risk score was engaged in another cohort, E-MTAB-1980 from the ArrayExpress dataset.ResultsThe mRNA and protein expression of MCM2-7 were increased in ccRCC compared with normal tissues. High MCM2, MCM4, MCM6 and MCM7 expression were associated with a poor prognosis of ccRCC patients. Functional enrichment analysis revealed that MCM2-7 might influence the progress of ccRCC by regulating the cell cycle. Knockdown of MCM7 can inhibit the proliferation of ccRCC cells. A two-gene risk score including MCM4 and MCM6 can predict overall survival (OS) of ccRCC patients. The risk score was successfully verified by further using Arrayexpress cohort.ConclusionWe analyze MCM2-7 mRNA and protein levels in ccRCC. MCM7 is determined to promote tumor proliferation. Meanwhile, our study has determined a risk score model composed of MCM2-7 can predict the prognosis of ccRCC patients, which may help future treatment strategies.

Project description:Clear cell renal cell carcinoma (ccRCC) is a commonly occurring and highly aggressive urological malignancy characterized by a significant mortality rate. Current therapeutic options for advanced ccRCC are limited, necessitating the discovery of novel biomarkers and therapeutic targets. Carboxypeptidase A4 (CPA4) is a zinc-containing metallocarboxypeptidase with implications in various cancer types, but its role in ccRCC remains unexplored. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized in order to investigate the differential expression patterns of CPA4. The expression of CPA4 in ccRCC patients was further verified using immunohistochemical (IHC) examination of 24 clinical specimens. A network of protein-protein interactions (PPI) was established, incorporating CPA4 and its genes that were expressed differentially. Functional enrichment analyses were conducted to anticipate the contribution of CPA4 in the development of ccRCC. To validate our earlier study, we conducted real-time PCR and cell functional tests on ccRCC cell lines. Our findings revealed that CPA4 is overexpressed in ccRCC, and the higher the expression of CPA4, the worse the clinical outcomes such as TNM stage, pathological stage, histological grade, etc. Moreover, patients with high CPA4 expression had worse overall survival, disease-specific survival and progress-free interval than patients with low expression. The PPI network analysis highlighted potential interactions contributing to ccRCC progression. Functional enrichment analysis indicated the involvement of CPA4 in the regulation of key pathways associated with ccRCC development. Additionally, immune infiltration analysis suggested a potential link between CPA4 expression and immune response in the tumour microenvironment. Finally, cell functional studies in ccRCC cell lines shed light on the molecular mechanisms underlying the role of CPA4 in promoting ccRCC formation. Overall, our study unveils CPA4 as a promising biomarker with prognostic potential in ccRCC. The identified interactions and pathways provide valuable insights into its implications in ccRCC development and offer a foundation for future research on targeted therapies. Further investigation of CPA4's involvement in immune responses may contribute to the development of immunotherapeutic strategies for ccRCC treatment.

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CDCA2 acts as an oncogene and induces proliferation of clear cell renal cell carcinoma cells.

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CDCA2 acts as an oncogene and induces proliferation of clear cell renal cell carcinoma cells.

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