基因敲除
癌症研究
肾细胞癌
细胞生长
肾透明细胞癌
细胞迁移
细胞
医学
免疫组织化学
RNA干扰
细胞凋亡
病理
生物
基因
核糖核酸
生物化学
遗传学
作者
Xuelian Pei,Muhan Li,Jun Zhan,Yu Yu,Xiaofan Wei,Lina Guan,Hakan Aydın,Paul Elson,Ming Zhou,Huiying He,Hongquan Zhang
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2015-04-28
卷期号:10 (4): e0124338-e0124338
被引量:35
标识
DOI:10.1371/journal.pone.0124338
摘要
Insulin-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.Caki-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.IMP3 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.IMP3 promotes RCC cell migration and invasion by activation of NF-кB pathway. IMP3 is validated to be an independent prognostic marker for localized CCRCC.
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