Enhanced IMP3 Expression Activates NF-кB Pathway and Promotes Renal Cell Carcinoma Progression.
Enhanced IMP3 Expression Activates NF-кB Pathway and Promotes Renal Cell Carcinoma Progression.
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IMP3 表达增强激活 NF-kappa B 通路并促进肾细胞癌进展
DOI：
10.1371/journal.pone.0124338
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Pei X;Li M;Zhan J;Yu Y;Wei X;Guan L;Aydin H;Elson P;Zhou M;He H;Zhang H
胰岛素样生长因子2 mRNA结合蛋白3（IMP3）在转移性和原发性肾细胞癌（RCC）中表达。然而，IMP3在RCC进展中的作用知之甚少。我们的目的是揭示IMP3在调节透明细胞肾细胞癌（CCRCC）进展中的机制，并验证IMP3在局部CCRCC中的预后意义。通过Transwell测定分析稳定过表达IMP 3的Caki-1细胞和敲低IMP 3的Achn细胞的细胞迁移和侵袭。RNA-seq用于分析表达IMP 3的Caki-1细胞中的基因表达。使用肿瘤组织阵列通过免疫组织化学检查469名局限性CCRCC患者的IMP3表达。IMP3促进Caki-1细胞的迁移和侵袭，而通过RNAi敲低IMP3抑制Achn细胞的迁移和侵袭。IMP3表达增强激活NF-κ B B通路，促进肾癌细胞迁移。IMP3在局部CCRCC中的表达与较高的核分级、较高的T分期、坏死和肉瘤样分化有关（p< 0.001）。增强的IMP3表达与较短的无复发生存期和总生存期相关。多因素分析证实IMP3是局限性CCRCC患者的独立预后因素。IMP3通过激活NF-B通路促进肾癌细胞迁移和侵袭。IMP3被证实是局限性CCRCC的独立预后标志物。
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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