SOCS6 Functions as a Tumor Suppressor by Inducing Apoptosis and Inhibiting Angiogenesis in Human Prostate Cancer
Dongbo Yuan1,2,3, Wei Wang2, Jiaming Su4
1Medical College of Guizhou University, Guizhou, 550025, China.
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.
Insights
Suppressor of cytokine signaling 6 (SOCS6) is downregulated in prostate cancer (PCa), correlating with advanced disease. Restoring SOCS6 inhibits PCa progression and may offer a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Previous studies linked reduced Suppressor of cytokine signaling 6 (SOCS6) expression to advanced human prostate cancer (PCa).
- Understanding SOCS6's role is crucial for developing new PCa treatments.
Purpose of the Study:
- To investigate the tumor-suppressive functions of SOCS6 in prostate cancer.
- To elucidate the molecular mechanisms underlying SOCS6's action in PCa.
Main Methods:
- Compared SOCS6 expression in PCa versus normal tissues via immunohistochemistry.
- Assessed correlations between SOCS6 levels and clinicopathological features/prognosis.
- Evaluated SOCS6's functional impact in vitro and in vivo, including apoptosis, migration, invasion, and angiogenesis.
- Identified SOCS6-regulated genes using RNA-sequencing and pathway analysis.
Main Results:
- Significantly lower SOCS6 expression correlated with advanced clinical stage and lymph node metastasis in PCa patients.
- SOCS6 served as an independent prognostic factor for disease-free survival.
- Overexpressing SOCS6 suppressed PCa cell invasion, migration, tumor growth, and angiogenesis, while inducing apoptosis.
- Mechanistically, SOCS6 downregulated Bcl2, Hspa1a, F7, Fak3, and Frzb.
Conclusions:
- Reduced SOCS6 expression predicts a poor prognosis in prostate cancer.
- SOCS6 functions as a tumor suppressor in PCa.
- SOCS6 represents a potential novel therapeutic target for prostate cancer.
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