Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Department of Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Anticancer Agents Med Chem. 2021;21(14):1835-1841. doi: 10.2174/1871520620666200731161810.
Prostate cancer is one of the most commonly diagnosed cancers and one of the most common causes of cancer-related deaths among men worldwide. Patients who are diagnosed with localized prostate cancer and treated with radical prostatectomy often respond well to therapy. The current standard therapy for prostate cancer involves maximal surgical resection, followed by radiotherapy and chemotherapy. Clarifying the molecular mechanism of tumor proliferation and recurrence becomes more and more important for clinical therapies of prostate cancer.
Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpress or knockdown the target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between the two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis.
In this study, we identified that FOXM1 expression was significantly enriched in prostate cancer compared with normal tissue. Additionally, FOXM1 was functionally required for tumor proliferation and its expression was associated with poor prognosis in prostate cancer patients. Mechanically, FOXM1-dependent regulation of EZH2 is essential for proliferation and progression in prostate cancer.
Taken together, our data suggest that oncogenic transcription factor FoxM1 is up-regulated in prostate cancer, suggesting that the growth of cancer cells may depend on FOXM1 activity. FOXM1 may serve as a clinical prognostic factor and a therapeutic target for prostate cancer.
前列腺癌是全球男性最常见的癌症之一，也是癌症相关死亡的最常见原因之一。被诊断为局限性前列腺癌并接受根治性前列腺切除术的患者通常对治疗反应良好。目前前列腺癌的标准治疗方法包括最大限度的手术切除，然后进行放疗和化疗。阐明肿瘤增殖和复发的分子机制对于前列腺癌的临床治疗越来越重要。
采用实时定量 PCR 和 Western blot 检测 mRNA 和蛋白表达。采用慢病毒感染过表达或敲低目的基因。采用流式细胞术分析检测蛋白表达和凋亡水平。采用免疫组织化学鉴定组织中蛋白的表达。采用双尾 t 检验评估两组间的统计学差异。采用单因素方差分析（ANOVA）比较多组间的差异，然后采用 Dunnett 事后检验进行多重比较。采用对数秩检验分析 Kaplan-Meier 生存曲线的统计学意义。
在这项研究中，我们发现 FOXM1 的表达在前列腺癌组织中明显富集，而在正常组织中则明显减少。此外，FOXM1 对肿瘤增殖具有功能性要求，其表达与前列腺癌患者的不良预后相关。在机制上，FOXM1 对 EZH2 的依赖性调节对于前列腺癌的增殖和进展至关重要。
综上所述，我们的数据表明，致癌转录因子 FoxM1 在前列腺癌中上调，提示癌细胞的生长可能依赖于 FOXM1 活性。FOXM1 可能成为前列腺癌的临床预后因素和治疗靶点。
