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Decreased Expression of MYPT1 Contributes to Tumor Angiogenesis and Poor Patient Prognosis in Human Prostate Cancer

[ Vol. 18 , Issue. 2 ]

Author(s):

Y. Liang, Y. Zhuo, Z. Lin, F. Jiang, Q. Dai, J. Lu, W. Dong, X. Zhu, Z. Han* and W. Zhong*   Pages 100 - 108 ( 9 )

Abstract:


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.

Keywords:

Prostate cancer, myosin phosphatase targeting subunit 1, prognosis, tumor angiogenesis, metastasis, anticancer therapy.

Affiliation:

Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510260, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180



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