Abstract
Lung cancer (LC) is a devastating malignancy with no effective treatments, due to its complex genomic profile. Using bioinformatics analysis and immunohistochemical of lung carcinoma tissues, we show that TRIM59 as a critical oncoprotein relating to LC proliferation and metastasis. In this study, high TRIM59 expression was significantly correlated with lymph node metastasis, distant metastasis, and tumour stage. Furthermore, up‐regulation of TRIM59 expression correlated with poorer outcomes in LC patients. Mechanistically, TRIM59 play a key role in promoting LC growth and metastasis through regulation of extracellular‐signal regulated protein kinase (ERK) signalling pathway and epithelial‐to‐mesenchymal transition (EMT)‐markers, as validated by loss‐of‐function studies. In‐depth bioinformatics analysis showed that there is preliminary evidence of co‐expression of TRIM59 and cyclin dependent kinase 6 (CDK6) in LC. Notably, CDK6 expression significantly decreased when TRIM59 was knocked down in the LC cells. In contrast, exogenous up‐regulation of TRIM59 expression also induced significant increases in the expression of CDK6. Moreover, the expression of CDK6 was also inhibited by the ERK signalling inhibitor, U0126. The results of both loss‐ and gain‐of‐function studies showed that TRIM59 could regulate the expression of CDK6. Collectively, these data provide evidence that TRIM59 is involved in lung carcinoma growth and progression possibly through the induction of CDK6 expression and EMT process by activation of ERK pathway.
Highlights
Lung cancer (LC), the leading cause of cancer‐related death worldwide, is characterized by a high metastatic capacity
Significant improvements have been made in the prediction of LC outcomes using clinical information, such as TNM staging, the heterogeneity of outcomes observed among patients with similar phenotypic properties indicates that genetic variations may play crucial roles in LC growth and metastasis.[2]
We investigated the correlation of TRIM59 expression and the clinicopathological parameters in lung carcinoma and determined whether TRIM59 was involved in the epithelial‐mesenchymal transition (EMT) process of LC by activation of the extracellular-signal regulated protein kinase (ERK) pathway
Summary
Lung cancer (LC), the leading cause of cancer‐related death worldwide, is characterized by a high metastatic capacity. Optimal window for surgery due to metastasis.[1] significant improvements have been made in the prediction of LC outcomes using clinical information, such as TNM staging, the heterogeneity of outcomes observed among patients with similar phenotypic properties indicates that genetic variations may play crucial roles in LC growth and metastasis.[2] The complicated molecular and cellular mechanisms involved in LC metastasis remain poorly understood. We further investigated the mechanisms that TRIM59 positively regulates CDK6 expression by activation of ERK pathway, which contribute to cancer cell growth and invasion
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