Overexpression of PDZ-binding kinase confers malignant phenotype in prostate cancer via the regulation of E2F1
Overexpression of PDZ-binding kinase confers malignant phenotype in prostate cancer via the regulation of E2F1
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PDZ 结合激酶的过度表达通过 E2F1 的调节赋予前列腺癌恶性表型
DOI：
10.1016/j.ijbiomac.2015.08.048
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发表时间：
2015-11-01
影响因子：
8.2
通讯作者：
Zhong, Wei-De
中科院分区：
文献类型：
--
作者：
Chen, Jia-Hong;Liang, Yu-Xiang;Zhong, Wei-De
细胞周期特异性转录因子E2 F1在前列腺癌（PCa）中的作用及其机制尚未完全阐明。为了解决这个问题，我们在这里确定PDZ结合激酶（PBK）作为E2 F1的直接目标，通过生物信息学结合位点预测，结合染色质免疫沉淀-PCR（ChIP-PCR），定量（Q）-PCR和Western blot分析。在体外实验中，我们观察到E2 F1和PI 3 K基因的敲低可以抑制PCa细胞系的增殖、侵袭和迁移。基于Taylor数据集，我们发现，随着患者年龄的增加，PCa患者的PBK上调更频繁（P = 0.044），Gleason评分越高（P < 0.001），临床病理分期晚期（P =0.019）、有无转移（P = 0.008）、总生存期（P < 0.001）和PSA阴性（P = 0.004）。更有趣的是，生存分析将PBK确定为预测PCa患者生化无复发生存的独立因素（P = 0.041）。综上所述，这些发现首次提供了令人信服的证据，即PBK的过表达可能通过E2 F1的调节导致PCa细胞的高度恶性表型。PBK可能作为一种生物标志物，可以区分患者的生化复发性和非生化复发性疾病后，根治性直肠癌切除术，突出其作为治疗靶点的潜力。(C)2015 Elsevier B. V.版权所有。
Roles and mechanisms of cell cycle-specific transcription factor E2F1 on prostate cancer (PCa) have not been fully elucidated. To address this problem, we here identified PDZ-binding kinase (PBK) as a direct target for E2F1 through bioinformatics binding site prediction, combined with chromatin immunoprecipitation-PCR (ChIP-PCR), quantitative (Q)-PCR and Western blot analysis. Then, we observed that the knockdown of both E2F1 and PBK could suppress cell proliferation, invasion and migration of PCa cell lines in vitro. Based on Taylor dataset, we found that PBK upregulation occurred more frequently in PCa patients with the older age of patients (P = 0.044), the higher Gleason score (P < 0.001), the advanced clinical pathological stage (P =0.019), the presence of metastasis (P = 0.008), the overall survival (P < 0.001) and PSA failure (P = 0.004). More interestingly, the survival analysis identified PBK as an independent factor for predicting the biochemical recurrence-free survival of PCa patients (P = 0.041). Taken together, these findings offer the convincing evidence for the first time that the overexpression of PBK may lead to high malignant phenotype in PCa cells via the regulation of E2F1. PBK may function as a biomarker that can differentiate patients with biochemical recurrent and non-biochemical recurrent disease following radical prostatectomy, highlighting its potential as a therapeutic target. (C) 2015 Elsevier B.V. All rights reserved.