Enhanced IMP3 expression activates NF-κB pathway and promotes renal cell carcinoma progression

Xuelian Pei, Muhan Li, Jun Zhan, Yu Yu, Xiaofan Wei, Lizhao Guan, Hakan Aydin, Paul Elson, Ming Zhou, Huiying He, Hongquan Zhang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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-κB 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-κB pathway. IMP3 is validated to be an independent prognostic marker for localized CCRCC.

Original languageEnglish (US)
Article numbere0124338
JournalPLoS One
Volume10
Issue number4
DOIs
StatePublished - Apr 28 2015

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Somatomedins
kidney cells
Renal Cell Carcinoma
Gene expression
carcinoma
Cell Movement
Tumors
Assays
Carrier Proteins
Chemical activation
Cells
RNA
Tissue
Messenger RNA
cell movement
cell invasion
cells
Insulin-Like Growth Factor Binding Protein 2
RNA Interference
Transcriptome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Pei, X., Li, M., Zhan, J., Yu, Y., Wei, X., Guan, L., ... Zhang, H. (2015). Enhanced IMP3 expression activates NF-κB pathway and promotes renal cell carcinoma progression. PLoS One, 10(4), [e0124338]. https://doi.org/10.1371/journal.pone.0124338

Enhanced IMP3 expression activates NF-κB pathway and promotes renal cell carcinoma progression. / Pei, Xuelian; Li, Muhan; Zhan, Jun; Yu, Yu; Wei, Xiaofan; Guan, Lizhao; Aydin, Hakan; Elson, Paul; Zhou, Ming; He, Huiying; Zhang, Hongquan.

In: PLoS One, Vol. 10, No. 4, e0124338, 28.04.2015.

Research output: Contribution to journalArticle

Pei, X, Li, M, Zhan, J, Yu, Y, Wei, X, Guan, L, Aydin, H, Elson, P, Zhou, M, He, H & Zhang, H 2015, 'Enhanced IMP3 expression activates NF-κB pathway and promotes renal cell carcinoma progression', PLoS One, vol. 10, no. 4, e0124338. https://doi.org/10.1371/journal.pone.0124338
Pei, Xuelian ; Li, Muhan ; Zhan, Jun ; Yu, Yu ; Wei, Xiaofan ; Guan, Lizhao ; Aydin, Hakan ; Elson, Paul ; Zhou, Ming ; He, Huiying ; Zhang, Hongquan. / Enhanced IMP3 expression activates NF-κB pathway and promotes renal cell carcinoma progression. In: PLoS One. 2015 ; Vol. 10, No. 4.
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abstract = "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-κB 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-κB pathway. IMP3 is validated to be an independent prognostic marker for localized CCRCC.",
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AU - Li, Muhan

AU - Zhan, Jun

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AU - Wei, Xiaofan

AU - Guan, Lizhao

AU - Aydin, Hakan

AU - Elson, Paul

AU - Zhou, Ming

AU - He, Huiying

AU - Zhang, Hongquan

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N2 - 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-κB 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-κB pathway. IMP3 is validated to be an independent prognostic marker for localized CCRCC.

AB - 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-κB 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-κB pathway. IMP3 is validated to be an independent prognostic marker for localized CCRCC.

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