摘要
背景:我们以前的研究表明,细胞因子信号抑制因子6(SOCS 6)的下调与前列腺癌(PCa)的恶性进展有关。 目的:探讨SOCS 6在PCA中的抑瘤作用及其机制。 方法:采用免疫组织化学方法检测前列腺癌和非癌性前列腺组织中SOCS 6的表达。SOCS 6表达与各种临床病理特征及PAT的相关性研究评估患者的预后。此外,我们还通过在体外过表达SOCS 6(细胞凋亡、迁移和侵袭试验)和体内(肿瘤形成、血管生成)来研究SOCS 6的功能。和凋亡)。此外,对SOCS 6调控基因进行了下代RNA测序分析、途径富集分析和体外实验验证。 结果:PCa患者SOCS 6表达下调与晚期临床分期(P=0.029)和淋巴结转移阳性(P=0.013)密切相关。我们还确认SOCS 6是一种独立的NT预后因素对PCa患者无病生存的影响(P=0.045)。此外,SOCS 6的过表达抑制了PCa细胞的侵袭、迁移、异种肿瘤的生长和血管生成,但诱导了肿瘤的发生。d细胞凋亡(P值<0.05)。我们发现SOCS 6的表达可以诱导细胞凋亡,同时抑制bcl 2和hspa1a的表达,抑制肿瘤血管生成。F7、Fak3和Frzb的下调。 结论:SOCS 6表达降低可能预示PCa预后不良。因此,SOCS 6可作为肿瘤抑制剂和新的治疗靶点。这种癌症。
关键词: 前列腺癌,细胞因子信号抑制因子6,肿瘤抑制因子,预后,侵袭表型,SOCS 6。
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
关键词: 前列腺癌,细胞因子信号抑制因子6,肿瘤抑制因子,预后,侵袭表型,SOCS 6。
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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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 |
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