Enhanced IMP3 Expression Activates NF-кB Pathway and Promotes Renal Cell Carcinoma Progression

PLoS One. 2015 Apr 28;10(4):e0124338. doi: 10.1371/journal.pone.0124338. eCollection 2015.

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-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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Disease Progression*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Prognosis
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • IGF2BP3 protein, human
  • NF-kappa B
  • RNA-Binding Proteins

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma

Grants and funding

This work was supported by the Natural Science Foundation of China 81001135, 81230051, 30830048, 31170711 and 81321003, the Ministry of Science and Technology of China 2013CB910501, 2010CB912203 and 2010CB529402, the 111 Project of the Ministry of Education, Beijing Natural Science Foundation 7120002 and Peking University grants BMU20120314 and BMU20130364, and a Leading Academic Discipline Project of Beijing Education Bureau. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.