Central Lab, The First Affiliated Hospital of Soochow University Suzhou, Jiangsu 215006, P.R. China.
Department of Oncology, The First People's Hospital of Yancheng, Yancheng, Jiangsu 224000, P.R. China.
Int J Oncol. 2016 Jul;49(1):381-92. doi: 10.3892/ijo.2016.3500. Epub 2016 Apr 25.
NF-κB subunits play important roles in carcinogenesis of a variety of human malignancies and response to cancer therapy; however, the contribution of an individual subunit has not been thoroughly defined. Constitutive activation of the canonical NF-κB subunit is a critical event in prostate carcinogenesis. Recent findings point out that RelB, which contributes to the non-canonical NF-κB activity, functions importantly in the prostate cancer progression. Here, we investigated systemically the functional roles of RelB in prostate cancer and examine its significance as a therapeutic target. Targeting RelB using short hairpin RNA approach in androgen-independent DU145 prostate cancer cells interfered with various biological behaviors of cells. We observed that RelB knockdown inhibited prostate cancer cell growth, migration, and invasion, and enhanced proteasome inhibitor sensitivity. The altered expression of anti-apoptotic gene Bcl-2 played critical roles in regulating both spontaneous and radiation-induced apoptosis in the presence of RelB knockdown. For the first time, we showed that RelB knockdown significantly attenuated the migration and invasion of DU145 prostate cancer cells, due to the reduction of integrin β-1. Collectively, we provided evidence that RelB functioned as an oncogene in prostate cancer. Developing a RelB-targeted therapeutic intervention, is valuable in treating advanced, metastatic prostate cancer.
NF-κB 亚基在多种人类恶性肿瘤的发生和对癌症治疗的反应中发挥重要作用；然而，个别亚基的贡献尚未得到彻底阐明。经典 NF-κB 亚基的组成性激活是前列腺癌发生的关键事件。最近的研究结果指出，有助于非经典 NF-κB 活性的 RelB 在前列腺癌进展中具有重要作用。在这里，我们系统地研究了 RelB 在前列腺癌中的功能作用，并研究了它作为治疗靶点的意义。在雄激素非依赖性 DU145 前列腺癌细胞中使用短发夹 RNA 方法靶向 RelB 会干扰细胞的各种生物学行为。我们观察到 RelB 敲低抑制了前列腺癌细胞的生长、迁移和侵袭，并增强了蛋白酶体抑制剂的敏感性。抗凋亡基因 Bcl-2 的表达改变在 RelB 敲低存在的情况下对自发和辐射诱导的细胞凋亡的调节起着关键作用。我们首次表明，RelB 敲低由于整合素 β-1 的减少而显著减弱了 DU145 前列腺癌细胞的迁移和侵袭。总之，我们提供的证据表明 RelB 在前列腺癌中起癌基因的作用。开发针对 RelB 的治疗干预措施对于治疗晚期转移性前列腺癌具有重要价值。
