Insulin-like growth factor II mRNA-binding protein 3 expression promotes tumor formation and invasion and predicts poor prognosis in oral squamous cell carcinoma

J Oral Pathol Med. 2011 Oct;40(9):699-705. doi: 10.1111/j.1600-0714.2011.01019.x. Epub 2011 Feb 25.

Abstract

Background: Insulin-like growth factor II mRNA-binding protein 3 (IGF2BP3), an oncofetal RNA-binding protein, has been implicated in the enhancement of proliferation and invasion in various cancers. This study aimed to investigate the clinical significance and functional role of IGF2BP3 expression in oral squamous cell carcinoma (OSCC).

Methods: IGF2BP3 expression in 93 OSCC patients was investigated using immunohistochemical staining and correlated with clinical parameters and patients' survival. The effect of IGF2BP3 on cell invasion ability was evaluated by RNA interference in OSCC cell line.

Results: High expression of IGF2BP3 in OSCC was significantly correlated with large tumor size and lymph node metastasis. Kaplan-Meier analysis revealed that oral cancer patients with high IGF2BP3 expression had a significantly lower 5-year survival (P = 0.0017). Multivariate analysis of clinical samples demonstrated IGF2BP3 to be an independent prognosis factor (P = 0.003). Moreover, the IGF2BP3 shRNA significantly suppressed the invasion ability of OSCC in vitro, and the knockdown of endogenous IGF2BP3 expression also inhibited tumor formation in vivo.

Conclusions: IGF2BP3 enhances cell invasion ability and tumorigenicity in human OSCC in vitro and in vivo. IGF2BP3 is an independent prognostic factor in patients with OSCC. Targeting of IGF2BP3 could potentially suppress the tumor growth and metastasis to improve the outcome of patients with OSCC.

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • Blotting, Western
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / secondary
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis / pathology
  • Male
  • Mouth Neoplasms / pathology*
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • RNA Interference / physiology
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / analysis*
  • RNA-Binding Proteins / genetics
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • IGF2BP3 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins