Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
Int Urol Nephrol. 2019 Sep;51(9):1517-1526. doi: 10.1007/s11255-019-02169-3. Epub 2019 Jun 12.
To investigate the role of Minichromosome maintenance protein 5 (MCM5) in the clinical prognosis and biological function of renal cell carcinoma (RCC).
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.
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.
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.
研究微小染色体维持蛋白 5(MCM5)在肾细胞癌(RCC)临床预后和生物学功能中的作用。
分析 Oncomine 数据库以确定 RCC 中 MCMs 的差异表达。通过免疫组织化学(IHC)评估总共 50 例 RCC 组织,并确定 MCM5 与临床病理特征之间的关联。应用 Kaplan-Meier 曲线和对数秩检验进行生存分析。进一步通过 Western blot 检测 RCC 组织和细胞系中 MCM5 的表达。为了探讨 MCM5 在 RCC 中的生物学功能,用 shRNA-MCM5 或 MCM5 转染 RCC 细胞系(786-0、769p)。通过 MTT 和集落形成实验评估细胞增殖。在裸鼠中生成肿瘤异种移植以确认 MCM5 对肿瘤生长的影响。
MCM5 在 RCC 组织中明显过表达;Oncomine 数据库、IHC 和 Western blot 均证实了这一结果。IHC 和 LinkedOmics 分析表明,MCM5 表达与病理分期、淋巴结状态、远处转移和 TNM 分期显著相关(p<0.05),但与性别、年龄、位置或肿瘤大小无关(p>0.05)。此外,高 MCM5 水平与 RCC 不良临床结局相关(p<0.05)。此外,MCM5 沉默抑制 RCC 细胞系增殖并减少 786-0 异种移植肿瘤生长;相反,MCM5 上调促进细胞增殖。
MCM5 过表达与 RCC 的恶性状态和不良预后相关。此外,MCM5 在增殖中起重要作用,可能是 RCC 的潜在预后标志物和新的治疗靶点。