SOCS6系列
血管生成
癌症研究
下调和上调
细胞凋亡
前列腺癌
癌症
转移
医学
抑制器
化学
内科学
基因
生物化学
作者
Dongbo Yuan,Wei Wang,Jiaming Su,Yongqiang Zhang,Boshi Luan,H Sgt Rao,Tianfei Cheng,Wei Zhang,Shiwei Xiao,Mingsheng Zhang,Funeng Jiang,Zhaolin Sun,Zhenyu Jia,Weide Zhong,Jianguo Zhu
出处
期刊:Current Cancer Drug Targets
[Bentham Science]
日期:2018-10-17
卷期号:18 (9): 894-904
被引量:20
标识
DOI:10.2174/1568009618666180102101442
摘要
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.
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