Department of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.
Department of Urology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.
J Cell Biochem. 2019 Apr;120(4):6709-6717. doi: 10.1002/jcb.27967. Epub 2018 Nov 2.
The inhibitor of growth 4 (ING4) is known as a tumor suppressor. The expressions of ING4 were markedly reduced in human renal clear cell carcinoma (ccRCC) tissues. However, the role of ING4 in renal cell carcinoma (RCC) remains unknown. The aim of the current study was to detect the ING4 expression level and its potential role in human RCC cell lines. Our results showed that ING4 was lowly expressed in human RCC cell lines compared with that in proximal tubular cell line. Ectopic overexpression of ING4 inhibited the proliferation, migration, and invasion properties, and as well as prevented epithelial-mesenchymal transition (EMT) phenotype of RCC cells. In addition, ING4 overexpression induced cell apoptosis and autophagy in RCC cells. Furthermore, ING4 overexpression suppressed the activation of PI3K/Akt pathway in RCC cells. The activator of PI3K/Akt, insulin-like growth factor 1, abolished the effects of ING4 on RCC cells. These findings indicated that ING4 presented anticancer activity in RCC cells. The effects of ING4 on RCC cells were mediated by regulating the PI3K/Akt pathway. These findings suggested that ING4 could be used for gene therapy of RCC.
抑生长因子 4(ING4)是一种肿瘤抑制因子。ING4 在人肾透明细胞癌(ccRCC)组织中的表达明显降低。然而,ING4 在肾细胞癌(RCC)中的作用尚不清楚。本研究旨在检测 ING4 在人 RCC 细胞系中的表达水平及其潜在作用。我们的结果表明,与近端肾小管细胞系相比,ING4 在人 RCC 细胞系中表达水平较低。ING4 的异位过表达抑制了 RCC 细胞的增殖、迁移和侵袭能力,并阻止了上皮-间充质转化(EMT)表型。此外,ING4 过表达诱导 RCC 细胞凋亡和自噬。此外,ING4 过表达抑制了 RCC 细胞中 PI3K/Akt 通路的激活。PI3K/Akt 的激活剂,胰岛素样生长因子 1,消除了 ING4 对 RCC 细胞的作用。这些发现表明 ING4 在 RCC 细胞中具有抗癌活性。ING4 通过调节 PI3K/Akt 通路对 RCC 细胞发挥作用。这些发现表明 ING4 可用于 RCC 的基因治疗。