Abstract
BackgroundBladder cancer is a frequently diagnosed urinary system tumor, whose mortality remains rising. Minichromosome maintenance eight homologous recombination repair factor (MCM8), a newly discovered MCM family member, has been shown to be required for DNA replication. Unfortunately, little is known concerning the roles of MCM8 in bladder cancer.MethodsThe present study, we aimed at probing into the impacts and detailed mechanisms of MCM8 in bladder cancer progression. In this study, MCM8 expression level was detected through immunohistochemistry staining (IHC), qRT-PCR and Western blot assay. Silenced MCM8 cell models were constructed by lentivirus transfection. In vitro, the cell proliferation was evaluated by the MTT assay. The wound-healing assay and the transwell assay were utilized to assess the cell migration. Also, the cell apoptosis and the cell cycle were determined by flow cytometry. Moreover, the Human Apoptosis Antibody Array assay was performed to analyze the alterations of apoptosis-related proteins. The in vivo experiments were conducted to verify the effects of MCM8 knockdown on the tumor growth of bladder cancer.ResultsThe results demonstrated that compared with normal adjacent tissues, MCM8 expression in bladder cancer tissues was strongly up-regulated. The up-regulation of MCM8 expression in bladder cancer may be a valuable independent prognostic indicator. Of note, MCM8 inhibition modulated the malignant phenotypes of bladder cancer cells. In terms of mechanism, it was validated that MCM8 knockdown made Akt, P-Akt, CCND1 and CDK6 levels down-regulated, as well as MAPK9 up-regulated.ConclusionsTaken together, our study demonstrated an important role of MCM8 in bladder cancer and created a rationale for the therapeutic potential of MCM8 inhibition in human bladder cancer therapy.
Highlights
Bladder cancer is a frequently diagnosed urinary system tumor, whose mortality remains rising
The expression pattern and significance of MCM8 in bladder cancer Initially, the differential expression of MCM8 analyses were performed on bladder cancer tumor tissues and adjacent normal tissues, which revealed 52.2% of bladder cancer tumor tissues with high MCM8 levels, while low MCM8 expression in all normal tissues (P < 0.001, Table 1, Fig. 1a)
The correlation between MCM8 expression and clinical characteristics was evaluated using the Mann–Whitney U analysis and the Pearson correlation analysis, which demonstrated that MCM8 expression was positively correlated with pathological grade with a P value of 0.001 (Table 2, Table 3), yet no significant correlation was observed between MCM8 expression and age, gender, tumor size, lymphadenopathy, stage or T Infiltrate (Table 2)
Summary
Bladder cancer is a frequently diagnosed urinary system tumor, whose mortality remains rising. Minichromosome maintenance eight homologous recombination repair factor (MCM8), a newly discovered MCM family member, has been shown to be required for DNA replication. Little is known concerning the roles of MCM8 in bladder cancer. The progress has been made in terms of immunotherapy and targeted therapies for bladder cancer [4, 5], improving the overall survival of patients is still a major clinical challenge. Identifying novel and effective therapeutic targets is essential for gaining a detailed understanding of the pathogenesis of bladder cancer and formulating more efficient molecular therapies strategies. Minichromosome maintenance eight homologous recombination repair factor (MCM8) and its physical partner MCM9 are two others newly discovered MCM family members, which have been shown to be required for DNA replication [11]. This study was aimed to explore the roles of MCM8 in bladder cancer
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