MYPT1 表达降低促进人前列腺癌肿瘤血管生成和患者预后不良。
Decreased Expression of MYPT1 Contributes to Tumor Angiogenesis and Poor Patient Prognosis in Human Prostate Cancer.
机构信息
Department of Urology, Guangzhou First People's Hospital, The Second Affliated Hospital of South China University of Technology, South China University of Technology, Guangzhou, Guangdong 510180, China.
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, China.
出版信息
Curr Mol Med. 2018;18(2):100-108. doi: 10.2174/1566524018666180705111342.
BACKGROUND
Our previous study demonstrated that Myosin Phosphatase Targeting subunit 1 (MYPT1) may function as a direct target of microRNA-30d, which promotes tumor angiogenesis and tumor growth of prostate cancer (PCa). Here, we aimed to investigate the clinical significance of MYPT1 expression and its functions in PCa.
METHODS
Roles of MYPT1 deregulation in tumor angiogenesis of PCa was determined in vitro and in vivo experiments. Expression patterns of MYPT1 and CD31 proteins were examined by immunohistochemistry and immunofluorescence, respectively. Associations of MYPT1/CD31 combination with various clinicopathological features and patients' prognosis of PCa were also statistically evaluated.
RESULTS
Through gain- and loss-of-function experiments, MYPT1 inhibited capillary tube formation of endothelial cells and in vivo tumor angiogenesis in a mouse model with the downregulation of VEGF and CD31 expression. In addition, MYPT1 expression was significantly decreased, while CD31 expression was dramatically increased in PCa tissues compared to benign prostate tissues. Notably, MYPT1 expression levels in PCa tissues were negatively correlated with that of CD31. Statistically, MYPT1-low/CD31- high expression was distinctly associated with high Gleason score, positive biochemical recurrence, and reduced overall survival of PCa patients. Moreover, PCa patients with MYPT1-low/CD31-high expression more frequently had shorter overall, biochemical recurrence-free and metastasis-free survivals. MYPT1/CD31 combination was identified as an independent factor to predict biochemical recurrence-free and metastasis-free survivals of PCa patients.
CONCLUSIONS
Our findings indicate that MYPT1 may inhibit angiogenesis and contribute favorable prognosis in PCa patients, implying that MYPT1 might be a potential drug candidate in anticancer therapy.
背景
我们之前的研究表明肌球蛋白磷酸酶靶向亚单位 1（MYPT1）可能作为 microRNA-30d 的直接靶标发挥作用，促进前列腺癌（PCa）的肿瘤血管生成和肿瘤生长。在这里，我们旨在研究 MYPT1 表达的临床意义及其在 PCa 中的功能。
方法
通过体外和体内实验确定 MYPT1 失调在 PCa 肿瘤血管生成中的作用。通过免疫组织化学和免疫荧光分别检测 MYPT1 和 CD31 蛋白的表达模式。还统计评估了 MYPT1/CD31 组合与 PCa 的各种临床病理特征和患者预后的关联。
结果
通过增益和失活实验，MYPT1 通过下调 VEGF 和 CD31 表达抑制内皮细胞的毛细血管管形成和体内肿瘤血管生成。此外，与良性前列腺组织相比，PCa 组织中的 MYPT1 表达明显降低，而 CD31 表达明显增加。值得注意的是，PCa 组织中 MYPT1 的表达水平与 CD31 呈负相关。统计学上，MYPT1 低/CD31-高表达与高 Gleason 评分、阳性生化复发和 PCa 患者总生存率降低明显相关。此外，MYPT1 低/CD31-高表达的 PCa 患者总生存期、生化无复发生存期和无转移生存期更短。MYPT1/CD31 组合被确定为预测 PCa 患者生化无复发生存期和无转移生存期的独立因素。
结论
我们的研究结果表明，MYPT1 可能抑制血管生成并为 PCa 患者带来良好的预后，这表明 MYPT1 可能是抗癌治疗的潜在药物候选物。
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