Jiangxi Medical College, Nanchang University, Nanchang 330006, PR China; Department of Urology, Jiangxi Cancer Hospital, Nanchang 330029, PR China.
Department of Urology, Jiangxi Cancer Hospital, Nanchang 330029, PR China.
Cell Signal. 2019 Apr;56:1-14. doi: 10.1016/j.cellsig.2018.11.016. Epub 2018 Nov 20.
As the most commonly occurring form of primary renal tumor, renal cell carcinoma (RCC) is a malignancy accompanied by a high mortality rate. 3-phosphoinositide-dependent protein kinase 1 (PDK1) has been established as a protein target and generated considerable interest in both the pharmaceutical and academia industry. The aim of the current study was to investigate the effect of si-PDK1 on the RCC cell apoptosis, proliferation, migration, invasion and epithelial mesenchymal transition (EMT) in connection with the PI3K-PDK1-Akt pathway. Microarray analysis from the GEO database was adopted to identify differentially expressed genes (DEGs) related to RCC, after which the positive expression of the PDK1 protein in tissue was determined accordingly. The optimal silencing si-RNA was subsequently selected and RCC cell lines 786-O and A498 were selected and transfected with either a si-PDK1 or activator of the PI3K-PDK1-Akt pathway for grouping purposes. The mRNA and protein expressions of PDK1, the PI3K-PDK1-Akt pathway-, EMT- and apoptosis-related genes were then evaluated. The effect of si-PDK1 on cell proliferation, apoptosis, invasion and migration was then analyzed. Through microarray analysis of GSE6344, GSE53757, GSE14762 and GSE781, PDK1 was examined. PDK1 was determined to be highly expressed in RCC tissues. Si-PDK1 exhibited marked reductions in relation to the mRNA and protein expression of PDK1, PI3K, AKT as well as Vimentin while elevated mRNA and protein expressions of E-cadherin were detected, which ultimately suggested that cell migration, proliferation and invasion had been inhibited coupled with enhanced levels of cell apoptosis. While a notable observation was made highlighting that the PI3K-PDK1-Akt pathway antagonized the effect of PDK1 silencing. Taken together, the key observations of this study provide evidence suggesting that high expressions of PDK1 are found in RCC, while highlighting that silencing PDK1 could inhibit RCC cell proliferation, migration, invasion and EMT by repressing the PI3K-PDK1-Akt pathway.
作为最常见的原发性肾肿瘤形式，肾细胞癌（RCC）是一种死亡率较高的恶性肿瘤。3-磷酸肌醇依赖性蛋白激酶 1（PDK1）已被确定为一个蛋白靶点，在制药和学术界都引起了极大的兴趣。本研究旨在探讨 si-PDK1 对 RCC 细胞凋亡、增殖、迁移、侵袭和上皮间质转化（EMT）的影响，并与 PI3K-PDK1-Akt 通路相关。通过 GEO 数据库的微阵列分析确定与 RCC 相关的差异表达基因（DEGs），然后确定 PDK1 蛋白在组织中的阳性表达。随后选择最佳的沉默 siRNA，并选择 RCC 细胞系 786-O 和 A498 进行转染，分别用 si-PDK1 或 PI3K-PDK1-Akt 通路激活剂进行分组。然后评估 PDK1、PI3K-PDK1-Akt 通路、EMT 和凋亡相关基因的 mRNA 和蛋白表达。然后分析 si-PDK1 对细胞增殖、凋亡、侵袭和迁移的影响。通过 GSE6344、GSE53757、GSE14762 和 GSE781 的微阵列分析，检查 PDK1。结果表明，PDK1 在 RCC 组织中高表达。与 PDK1、PI3K、AKT 和波形蛋白的 mRNA 和蛋白表达相比，si-PDK1 显著降低，而 E-钙黏蛋白的 mRNA 和蛋白表达升高，这最终表明细胞迁移、增殖和侵袭受到抑制，同时细胞凋亡水平升高。值得注意的是，PI3K-PDK1-Akt 通路拮抗了 PDK1 沉默的作用。综上所述，本研究的主要观察结果表明，PDK1 在 RCC 中高表达，而沉默 PDK1 可通过抑制 PI3K-PDK1-Akt 通路抑制 RCC 细胞增殖、迁移、侵袭和 EMT。
