Abstract
BackgroundInsulin-like growth factor 2 mRNA binding protein 3 (IMP3) is expressed in metastatic and a subset of primary renal cell carcinoma (RCC). However, the role of IMP3 in RCC progression was poorly understood. We aim to uncover the mechanism of IMP3 in regulating clear cell RCC (CCRCC) progression and validate the prognostic significance of IMP3 in localized CCRCC.MethodsCaki-1 cells stably overexpressing IMP3 and Achn cells with knockdown of IMP3 were analyzed for cell migration and invasion by Transwell assay. RNA-seq was used to profile gene expression in IMP3-expressing Caki-1 cells. A cohort of 469 localized CCRCC patients were examined for IMP3 expression by immunohistochemistry using tumor tissue array.ResultsIMP3 promoted Caki-1 cell migration and invasion, whereas knockdown of IMP3 by RNAi inhibited Achn cell migration and invasion. Enhanced IMP3 expression activated NF-кB pathway and through which, it functioned in promoting the RCC cell migration. IMP3 expression in localized CCRCC was found to be associated with higher nuclear grade, higher T stage, necrosis and sarcomatoid differentiation (p< 0.001). Enhanced IMP3 expression was correlated with shorter recurrence-free and overall survivals. Multivariable analysis validated IMP3 as an independent prognostic factor for localized CCRCC patients.ConclusionIMP3 promotes RCC cell migration and invasion by activation of NF-кB pathway. IMP3 is validated to be an independent prognostic marker for localized CCRCC.
Highlights
Renal cell carcinoma (RCC), being the 6th leading cancer in men in the US, contributing to the estimated 63,920 newly diagnosed and 13,860 deaths from kidney cancer in 2014 [1]
We have demonstrated that IMP3 significantly promoted clear cell RCC (CCRCC) cell migration and invasion via a mechanism by which IMP3 activates NF-κB pathway
We found that IMP3 expression was significantly associated with the stage and survival of localized CCRCC patients using tissue microarray, indicating that IMP3 is involved in CCRCC progression
Summary
Renal cell carcinoma (RCC), being the 6th leading cancer in men in the US, contributing to the estimated 63,920 newly diagnosed and 13,860 deaths from kidney cancer in 2014 [1]. The incidence of RCC has been steadily rising by 2–4% each year. In China, limited studies showed there is obvious increment of the RCC morbidity in recent years with the increasing of early diagnosed cases. Insulin-like growth factor 2 mRNA binding protein 3 (IMP3) is expressed in metastatic and a subset of primary renal cell carcinoma (RCC). The role of IMP3 in RCC progression was poorly understood. We aim to uncover the mechanism of IMP3 in regulating clear cell RCC (CCRCC) progression and validate the prognostic significance of IMP3 in localized CCRCC
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