Abstract
Background: Our previous studies revealed that the downregulation of Suppressor of cytokine signaling 6 (SOCS6) was correlated with malignant progression of human prostate cancer (PCa).
Aims: In the current study, we aimed to investigate the tumor suppressive roles of SOCS6 and the underlying mechanisms in PCa.
Methods: SOCS6 expression in PCa and non-cancerous prostate tissues was compared by immunohistochemistry. Statistical associations of SOCS6 expression with various clinicopathological features and patients prognosis were evaluated. In addition, we investigated SOCS6’s functions by overexpressing it in vitro (cell apoptosis, migration and invasion assays) and in vivo (tumor formation, angiogenesis and apoptosis). Moreover, SOCS6-regulated genes were identified by nextgeneration RNA-sequencing analysis, followed by pathway enrichment analysis and in vitro experimental validation.
Results: SOCS6 downregulation was significantly associated with advanced clinical stage (P=0.029) and positive lymph node metastasis (P=0.013) in PCa patients. We also identified SOCS6 as an independent prognostic factor for disease-free survival in PCa patients (P=0.045). Moreover, overexpression of SOCS6 inhibited PCa cell invasion, migration, tumor xenografts growth and angiogenesis, but induced PCa cell apoptosis (P values <0.05). Mechanically, we revealed that SOCS6 expression may induce cell apoptosis coincident with down-regulation of Bcl2 and Hspa1a, and may suppress tumor angiogenesis with downregulation of F7, Fak3 and Frzb.
Conclusion: These findings suggest that the reduced expression of SOCS6 may be predictive of unfavorable prognosis in PCa. Thus, SOCS6 may serve as a tumor suppressor and a novel therapeutic target for this cancer.
Keywords: Prostate cancer, suppressor of cytokine signaling 6, tumor suppressor, prognosis, aggressive phenotype, SOCS6.
Current Cancer Drug Targets
Title:SOCS6 Functions as a Tumor Suppressor by Inducing Apoptosis and Inhibiting Angiogenesis in Human Prostate Cancer
Volume: 18 Issue: 9
Author(s): Dongbo Yuan, Wei Wang, Jiaming Su, Yongqiang Zhang, Boshi Luan, Haofu Rao, Tianfei Cheng, Wei Zhang, Shiwei Xiao, Mingsheng Zhang, Fu-Neng Jiang, Zhaolin Sun, Zhenyu Jia*, Wei-De Zhong*Jianguo Zhu*
Affiliation:
- Department of Plant and Botany Sciences, University of California of Riverside, Riverside, CA 92521,United States
- Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People`s Hospital, Guangzhou Medical University, Guangzhou 510180,China
- Department of Urology, Guizhou Provincial People`s Hospital, The Affiliated Hospital of Guizhuo Medical University, Guizhou, 550002,China
Keywords: Prostate cancer, suppressor of cytokine signaling 6, tumor suppressor, prognosis, aggressive phenotype, SOCS6.
Abstract: Background: Our previous studies revealed that the downregulation of Suppressor of cytokine signaling 6 (SOCS6) was correlated with malignant progression of human prostate cancer (PCa).
Aims: In the current study, we aimed to investigate the tumor suppressive roles of SOCS6 and the underlying mechanisms in PCa.
Methods: SOCS6 expression in PCa and non-cancerous prostate tissues was compared by immunohistochemistry. Statistical associations of SOCS6 expression with various clinicopathological features and patients prognosis were evaluated. In addition, we investigated SOCS6’s functions by overexpressing it in vitro (cell apoptosis, migration and invasion assays) and in vivo (tumor formation, angiogenesis and apoptosis). Moreover, SOCS6-regulated genes were identified by nextgeneration RNA-sequencing analysis, followed by pathway enrichment analysis and in vitro experimental validation.
Results: SOCS6 downregulation was significantly associated with advanced clinical stage (P=0.029) and positive lymph node metastasis (P=0.013) in PCa patients. We also identified SOCS6 as an independent prognostic factor for disease-free survival in PCa patients (P=0.045). Moreover, overexpression of SOCS6 inhibited PCa cell invasion, migration, tumor xenografts growth and angiogenesis, but induced PCa cell apoptosis (P values <0.05). Mechanically, we revealed that SOCS6 expression may induce cell apoptosis coincident with down-regulation of Bcl2 and Hspa1a, and may suppress tumor angiogenesis with downregulation of F7, Fak3 and Frzb.
Conclusion: These findings suggest that the reduced expression of SOCS6 may be predictive of unfavorable prognosis in PCa. Thus, SOCS6 may serve as a tumor suppressor and a novel therapeutic target for this cancer.
Export Options
About this article
Cite this article as:
Yuan Dongbo , Wang Wei, Su Jiaming , Zhang Yongqiang, Luan Boshi , Rao Haofu , Cheng Tianfei, Zhang Wei , Xiao Shiwei, Zhang Mingsheng , Jiang Fu-Neng, Sun Zhaolin , Jia Zhenyu *, Zhong Wei-De *, Zhu Jianguo*, SOCS6 Functions as a Tumor Suppressor by Inducing Apoptosis and Inhibiting Angiogenesis in Human Prostate Cancer, Current Cancer Drug Targets 2018; 18 (9) . https://dx.doi.org/10.2174/1568009618666180102101442
DOI https://dx.doi.org/10.2174/1568009618666180102101442 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- 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
-
Nanotechnological Strategies to Improve Water Solubility of Commercially Available Drugs
Current Nanomedicine Role of Protein Tyrosine Phosphatases in Plants
Current Genomics Role of Endogenous Androgen Against Insulin Resistance and Athero-sclerosis in Men with Type 2 Diabetes
Current Diabetes Reviews Oncotarget Strategies For Herpes Simplex Virus-1
Current Gene Therapy Role of PARP Inhibitors in Cancer Biology and Therapy
Current Medicinal Chemistry Therapeutic Targeting of Apoptotic Pathways in Cancer
Current Drug Targets Novel Anti-Prostate Cancer Curcumin Analogues That Enhance Androgen Receptor Degradation Activity
Anti-Cancer Agents in Medicinal Chemistry The Therapeutic Potential of Cell-Internalizing Aptamers
Current Topics in Medicinal Chemistry Synthesis and Antiproliferative Activity of 2-arylidene 6-(2-aryl-2-oxoethoxy)Benzofuran-3-one Derivatives
Letters in Drug Design & Discovery Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery Treatment of Estrogen Receptor-Positive Breast Cancer
Current Medicinal Chemistry A Novel Synthesis Method of Apogossypolone and its Antitumor Activity
Letters in Drug Design & Discovery A New Era of Immunotherapy in Prostate Cancer
Current Molecular Pharmacology MtDNA As a Cancer Marker: A Finally Closed Chapter?
Current Genomics Planning of External Beam Radiotherapy for Prostate Cancer Guided by PET/CT
Current Radiopharmaceuticals Growth Responses Following a Single Intra-Muscular hGH Plasmid Administration Compared to Daily Injections of hGH in Dwarf Mice
Current Gene Therapy Relationship between Gut Microbiota, Gut Hyperpermeability and Obesity
Current Medicinal Chemistry The Interaction of Dietary Fibres with the Colon
Current Nutrition & Food Science Effects of the Natural Isoflavonoid Genistein on Growth, Signaling Pathways and Gene Expression of Matrix Macromolecules by Breast Cancer Cells
Mini-Reviews in Medicinal Chemistry Pharmacogenetics of Drug Transporters and Its Impact on the Pharmacotherapy
Current Topics in Medicinal Chemistry