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.

中文翻译：

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PDK1的低表达通过抑制PI3K-PDK1-Akt途径来抑制肾癌细胞的增殖，迁移，侵袭和上皮间质转化。

肾细胞癌（RCC）作为原发性肾肿瘤的最常见形式，是伴随高死亡率的恶性肿瘤。3-磷酸​​肌醇依赖性蛋白激酶1（PDK1）已被确定为蛋白质靶标，在制药和学术界都引起了极大的兴趣。本研究的目的是研究si-PDK1与PI3K-PDK1-Akt途径相关的对RCC细胞凋亡，增殖，迁移，侵袭和上皮间充质转化（EMT）的影响。采用来自GEO数据库的微阵列分析来鉴定与RCC相关的差异表达基因（DEG），然后据此确定PDK1蛋白在组织中的阳性表达。随后选择最佳沉默的si-RNA，选择RCC细胞系786-O和A498，并用si-PDK1或PI3K-PDK1-Akt途径的激活剂转染，以进行分组。然后评估PDK1，PI3K-PDK1-Akt通路，EMT和凋亡相关基因的mRNA和蛋白质表达。然后分析了si-PDK1对细胞增殖，凋亡，侵袭和迁移的影响。通过对GSE6344，GSE53757，GSE14762和GSE781的微阵列分析，检查了PDK1。确定PDK1在RCC组织中高表达。Si-PDK1与PDK1，PI3K，AKT以及波形蛋白的mRNA和蛋白表达显着降低，而检测到E-钙粘蛋白的mRNA和蛋白表达却升高，这最终表明细胞迁移，增殖和侵袭已被抑制，同时细胞凋亡水平提高。尽管进行了显着观察，但突出表明PI3K-PDK1-Akt途径拮抗了PDK1沉默的作用。综上所述，这项研究的主要观察结果提供了证据，表明在RCC中发现了PDK1的高表达，同时强调了沉默PDK1可以通过抑制PI3K-PDK1-Akt途径抑制RCC细胞的增殖，迁移，侵袭和EMT。