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学科主题: 基础医学
题名:
Enhanced IMP3 Expression Activates NF-kappa B Pathway and Promotes Renal Cell Carcinoma Progression
作者: Pei, Xuelian1,2,4,7,8; Li, Muhan1,2,3; Zhan, Jun1,2,4; Yu, Yu1,2,4; Wei, Xiaofan1,2,4; Guan, Lizhao1,2,4; Aydin, Hakan5; Elson, Paul6; Zhou, Ming5; He, Huiying1,2,3; Zhang, Hongquan1,2,4
刊名: PLOS ONE
发表日期: 2015-04-28
DOI: 10.1371/journal.pone.0124338
卷: 10, 期:4
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: GROWTH-FACTOR II ; PREDICT METASTASIS ; PROTEIN IMP3 ; CANCER ; PROGNOSIS ; MIGRATION ; MARKER ; ADENOCARCINOMA ; BIOMARKER ; PROLIFERATION
英文摘要:

Background

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.

Methods

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.

Results

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-kappa B 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.

Conclusion

IMP3 promotes RCC cell migration and invasion by activation of NF-kappa B pathway. IMP3 is validated to be an independent prognostic marker for localized CCRCC.

语种: 英语
所属项目编号: 81001135 ; 81230051 ; 30830048 ; 31170711 ; 81321003 ; 2013CB910501 ; 2010CB912203 ; 2010CB529402 ; 7120002 ; BMU20120314 ; BMU20130364
项目资助者: Natural Science Foundation of China ; Ministry of Science and Technology of China ; Ministry of Education ; Beijing Natural Science Foundation ; Peking University ; Beijing Education Bureau
WOS记录号: WOS:000353659400046
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60019
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Peking Univ, Dept Pathol, Hlth Sci Ctr, Beijing 100871, Peoples R China
2.Cleveland Clin, Inst Pathol & Lab Med, Cleveland, OH 44106 USA
3.Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA
4.Peking Univ, Key Lab Carcinogenesis & Translat Res, Minist Educ, Hlth Sci Ctr, Beijing 100871, Peoples R China
5.Peking Univ, State Key Lab Nat & Biomimet Drugs, Hlth Sci Ctr, Beijing 100871, Peoples R China
6.Peking Univ, Dept Anat Histol & Embryol, Hlth Sci Ctr, Beijing 100871, Peoples R China
7.Shihezi Univ, Sch Med, Dept Histol & Embryol, Minist Educ, Shihezi, Xinjiang, Peoples R China
8.Shihezi Univ, Sch Med, Key Lab Xinjiang Endem & Ethn Dis, Minist Educ, Shihezi, Xinjiang, Peoples R China

Recommended Citation:
Pei, Xuelian,Li, Muhan,Zhan, Jun,et al. Enhanced IMP3 Expression Activates NF-kappa B Pathway and Promotes Renal Cell Carcinoma Progression[J]. PLOS ONE,2015,10(4).
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