Abstract：
Interleukin-6 (IL-6) is involved in the activation of several oncogenic pathways in prostate cancer. However, its upstream trans-signaling pathway remains largely unknown. This work proposes a mechanistic explanation of IL-6\'s upstream effectors in prostate carcinogenesis.
Samples were harvested to validate the expression of EZH2, miR-26a-5p, and IL-6. Moreover, the protein and its phosphorylation of STAT3 (signal transducer and transcription activator 3) were assessed in prostate cancer cells. We explored the effects of these effectors on malignant phenotypes in vitro and tumor growth in vivo using functional assays. Bioinformatics analysis, dual-luciferase reporter gene assays, and chromatin immunoprecipitation (ChIP) assays were used to determine their binding relationships.
Overexpression of EZH2 and IL-6, and under expression of miR-26a-5p was observed in prostate cancer. Silencing IL-6 repressed STAT3 to suppress the malignant phenotypes of prostate cancer cells. Mechanistically, EZH2 inhibited miR-26a-5p expression by promoting H3K27 histone methylation, and miR-26a-5p restricted the malignant phenotypes of prostate cancer by targeting IL-6. Ectopic EZH2 expression reduced xenograft growth by inhibiting miR-26a-5p and activating the IL-6/STAT3 axis.
EZH2 May potentially be involved in regulating its expression by recruiting H3K27me3 to the miR-26a-5p promoter region, which could further impact the IL6/STAT3 pathway.
Samples were harvested to validate the expression of EZH2, miR-26a-5p, and IL-6. Moreover, the protein and its phosphorylation of STAT3 (signal transducer and transcription activator 3) were assessed in prostate cancer cells. We explored the effects of these effectors on malignant phenotypes in vitro and tumor growth in vivo using functional assays. Bioinformatics analysis, dual-luciferase reporter gene assays, and chromatin immunoprecipitation (ChIP) assays were used to determine their binding relationships.
Overexpression of EZH2 and IL-6, and under expression of miR-26a-5p was observed in prostate cancer. Silencing IL-6 repressed STAT3 to suppress the malignant phenotypes of prostate cancer cells. Mechanistically, EZH2 inhibited miR-26a-5p expression by promoting H3K27 histone methylation, and miR-26a-5p restricted the malignant phenotypes of prostate cancer by targeting IL-6. Ectopic EZH2 expression reduced xenograft growth by inhibiting miR-26a-5p and activating the IL-6/STAT3 axis.
EZH2 May potentially be involved in regulating its expression by recruiting H3K27me3 to the miR-26a-5p promoter region, which could further impact the IL6/STAT3 pathway.
摘要：
■白细胞介素-6(IL-6)参与前列腺癌中几种致癌途径的激活。然而,其上游反式信号通路在很大程度上仍然未知。这项工作提出了IL-6上游效应在前列腺癌发生中的机制解释。
■收集样品以验证EZH2，miR-26a-5p的表达，IL-6此外，在前列腺癌细胞中评估STAT3(信号转导和转录激活因子3)的蛋白质及其磷酸化.我们使用功能测定探索了这些效应子对体外恶性表型和体内肿瘤生长的影响。生物信息学分析，双荧光素酶报告基因测定，和染色质免疫沉淀(ChIP)测定用于确定它们的结合关系。
■在前列腺癌中观察到EZH2和IL-6的过表达和miR-26a-5p的过表达。沉默IL-6抑制STAT3以抑制前列腺癌细胞的恶性表型。机械上,EZH2通过促进H3K27组蛋白甲基化抑制miR-26a-5p表达,miR-26a-5p通过靶向IL-6限制前列腺癌的恶性表型。异位EZH2表达通过抑制miR-26a-5p和激活IL-6/STAT3轴来降低异种移植物生长。
■EZH2可能通过将H3K27me3募集到miR-26a-5p启动子区来参与调节其表达，这可能进一步影响IL6/STAT3通路。
■收集样品以验证EZH2，miR-26a-5p的表达，IL-6此外，在前列腺癌细胞中评估STAT3(信号转导和转录激活因子3)的蛋白质及其磷酸化.我们使用功能测定探索了这些效应子对体外恶性表型和体内肿瘤生长的影响。生物信息学分析，双荧光素酶报告基因测定，和染色质免疫沉淀(ChIP)测定用于确定它们的结合关系。
■在前列腺癌中观察到EZH2和IL-6的过表达和miR-26a-5p的过表达。沉默IL-6抑制STAT3以抑制前列腺癌细胞的恶性表型。机械上,EZH2通过促进H3K27组蛋白甲基化抑制miR-26a-5p表达,miR-26a-5p通过靶向IL-6限制前列腺癌的恶性表型。异位EZH2表达通过抑制miR-26a-5p和激活IL-6/STAT3轴来降低异种移植物生长。
■EZH2可能通过将H3K27me3募集到miR-26a-5p启动子区来参与调节其表达，这可能进一步影响IL6/STAT3通路。
