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.
Current Molecular Medicine
Title:Decreased Expression of MYPT1 Contributes to Tumor Angiogenesis and Poor Patient Prognosis in Human Prostate Cancer
Volume: 18 Issue: 2
Author(s): Y. Liang, Y. Zhuo, Z. Lin, F. Jiang, Q. Dai, J. Lu, W. Dong, X. Zhu, Z. Han*W. Zhong*
Affiliation:
- Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, 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
Keywords: Prostate cancer, myosin phosphatase targeting subunit 1, prognosis, tumor angiogenesis, metastasis, anticancer therapy.
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.
Export Options
About this article
Cite this article as:
Liang Y. , Zhuo Y. , Lin Z., Jiang F. , Dai Q. , Lu J. , Dong W. , Zhu X. , Han Z. *, Zhong W. *, Decreased Expression of MYPT1 Contributes to Tumor Angiogenesis and Poor Patient Prognosis in Human Prostate Cancer, Current Molecular Medicine 2018; 18 (2) . https://dx.doi.org/10.2174/1566524018666180705111342
DOI https://dx.doi.org/10.2174/1566524018666180705111342 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Recent Advances in PUVA Photochemotherapy and PDT for the Treatment of Cancer
Current Pharmaceutical Design Human Reduced Folate Carrier Gene and Transcript Variants: Functional, Physiologic, and Pharmacologic Consequences
Current Pharmacogenomics Targeting Oncogenes and Tumor Suppressors genes to Mitigate Chemoresistance
Current Cancer Drug Targets Therapeutic Vaccines Explored in Patients with Non-Small Cell Lung Cancer
Anti-Cancer Agents in Medicinal Chemistry Effect of Environmental Contaminants on Mammalian Testis
Current Molecular Pharmacology Focal Adhesion Kinase as a Cancer Therapy Target
Anti-Cancer Agents in Medicinal Chemistry Role of Estradiol and Progesterone in HIV Susceptibility and Disease Progression
Mini-Reviews in Medicinal Chemistry Potential Clinical Applications of Multi-functional Milk Proteins and Peptides in Cancer Management
Current Medicinal Chemistry Viral Vectors for Gene-Directed Enzyme Prodrug Therapy
Current Gene Therapy Unravelling the Power of Omics for the Infertile Aging Male
Current Pharmaceutical Design Toxins Targeting Voltage-Activated Ca<sup>2+</sup> Channels and their Potential Biomedical Applications
Current Topics in Medicinal Chemistry Gene Expression Analysis Approach to Establish Possible Links Between Parkinson's Disease, Cancer and Cardiovascular Diseases
CNS & Neurological Disorders - Drug Targets MicroRNAs in Cancer Stem Cells: New Regulators of Stemness
Current Pharmaceutical Design Development of Method for Three-Point Data Estimation and SVR-QSAR Model to Screen Anti Cancer Leads
Combinatorial Chemistry & High Throughput Screening Synthesis, Antiproliferative, and Antiangiogenic Activities of Benzochromene and Benzoquinoline Derivatives on Prostate Cancer in vitro
Letters in Drug Design & Discovery Nanomedicine based on Nucleic Acids: Pharmacokinetic and Pharmacodynamic Perspectives
Current Pharmaceutical Biotechnology Melatonin as a Selective Estrogen Enzyme Modulator
Current Cancer Drug Targets Engineered Liposomes for Drug Delivery and Biomedical Imaging
Recent Patents on Nanomedicine Pharmacokinetic Distribution of 67Cu(II)2[3,5-Diisopropyl(Carboxy- 14C)Salicylate]4 Among Murine Tissues
Current Medicinal Chemistry Drug-Mediated Targeted Disruption of Multiple Protein Activities Through Functional Inhibition of the Hsp90 Chaperone Complex
Current Medicinal Chemistry