4.4 Article

MCM5 promotes tumour proliferation and correlates with the progression and prognosis of renal cell carcinoma

Journal

INTERNATIONAL UROLOGY AND NEPHROLOGY
Volume 51, Issue 9, Pages 1517-1526

Publisher

SPRINGER
DOI: 10.1007/s11255-019-02169-3

Keywords

MCM5; Renal cell carcinoma; Proliferation; Prognosis

Funding

  1. National Natural Science Foundation of China (NSFC) [81460137]

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Background To investigate the role of Minichromosome maintenance protein 5 (MCM5) in the clinical prognosis and biological function of renal cell carcinoma (RCC). Methods The Oncomine database was analysed to determine the differential expression of MCMs in RCC. A total of 50 RCC tissues were evaluated by immunohistochemistry (IHC), and the association between MCM5 and clinicopathologic features was determined. Kaplan-Meier curves and the log-rank test were applied for survival analysis. MCM5 expression in RCC tissues and cell lines was examined further by Western blotting. To explore the biological function of MCM5 in RCC, RCC cell lines (786-0, 769p) were transfected with shRNA-MCM5 or MCM5. Cell proliferation was assessed using MTT and colony-formation assays. Tumour xenografts were generated in nude mice to confirm the effects of MCM5 on tumour growth. Results MCM5 was significantly overexpressed in RCC tissues; this outcome was confirmed by the Oncomine database, IHC and Western blotting. IHC and LinkedOmics analysis demonstrated that the MCM5 expression was significantly associated with pathological stage, lymph node status, distant metastasis, and TNM stage (p < 0.05) but not with sex, age, position, or tumour size (p > 0.05). Furthermore, high MCM5 levels correlated with unfavourable clinical outcomes in RCC (p < 0.05). Additionally, MCM5 silencing inhibited RCC cell line proliferation and reduced 786-0 xenograft tumour growth; in contrast, MCM5 upregulation promoted cell proliferation. Conclusion MCM5 overexpression is associated with malignant status and poor prognosis in RCC. Additionally, MCM5 plays an important role in proliferation and may be a potential prognostic marker and novel therapeutic target for RCC.

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