Abstract
General control non-derepressible 5 (GCN5) is ectopically expressed in different types of human cancer and association with the carcinogenesis, development, and poor prognosis of cancers. The present study was aimed to investigate the potential role and related mechanisms of GCN5 in IL-6–treated prostate cancer (PCa) cell. The results showed that an elevated GCN5 expression was stimulated by IL-6. Knockdown of GCN5 significantly inhibited IL-6–driven proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, early growth response-1 (Egr-1) expression was elevated by IL-6 treatment and GCN5 siRNA down-regulated the expression of Egr-1. Furthermore, overexpression of Egr-1 attenuated the effects of GCN5 silence on cell proliferation, migration, invasion, and EMT in PCa. Besides, knockdown of GCN5 resulted in the down-regulation of p-Akt and up-regulation of PTEN, which was partly impeded by Egr-1 overexpression. The effects of GCN5 overexpression on cell proliferation and invasion were suppressed by LY294002, In conclusion, these data demonstrated the negative effect of up-regulated GCN5 in IL-6-induced metastasis and EMT in PCa cells through PI3K/PTEN/Akt signaling pathway down-regulating Egr-1 expression.
Highlights
Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related death worldwide in male [1]
Results revealed that General control non-derepressible 5 (GCN5) mRNA expression level was significantly up-regulated by IL-6 stimulation in the whole PCa cell lines, in which LNCaP cell line showed a maximum induction (Figure 1A)
Patients treated with chemotherapies display characteristic progression, the therapeutics of PCa were still impeded due to the complex molecular mechanism involved in the carcinogenesis, development, and metastasis of cancer
Summary
Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related death worldwide in male [1]. Substantial evidence has demonstrated that inflammation plays a critical role in the pathogenesis of PCa by regulating tumor microenvironment through releasing proinflammatory cytokines and growth factors, and modulating the tumor growth, progression, and metastasis [2,3,4]. It is very important to understand the molecular pathway associated with metastasis and inflammation for improving approaches to therapy and prevention of PCa. Interleukin (IL)-6 is a potent proinflammatory cytokine that exhibits functional pleiotropy in the regulation of growth, metastasis, and differentiation in numerous human cancers such as lung cancer, head and neck squamous cell carcinoma, breast, and PCa [5,6,7,8].
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