Increased IGF2BP3 expression promotes the aggressive phenotypes of colorectal cancer cells in vitro and vivo

J Cell Physiol. 2019 Aug;234(10):18466-18479. doi: 10.1002/jcp.28483. Epub 2019 Mar 20.

Abstract

Previous literatures reported insulin-like growth factor-2 messenger RNA-binding protein 3 (IGF2BP3) is a poor prognostic marker for colorectal cancer (CRC) patients. However, basic research on the effect and biological role of IGF2BP3 in CRC was still scare. Real-time quantitative polymerase chain reaction and western blot analysis were used to examine IGF2BP3 expression level in tumors and paired normal tissues from CRC patients. Tissue microarrays with 192 CRC patients were subjected to immunohistochemical staining to analyze the prognostic value of IGF2BP3. Proliferation assays, migration assays, and xenograft tumor formation in nude mice were performed to assess the biological role of IGF2BP3 in CRC cells. IGF2BP3 expression was significantly upregulated in tumor tissues compared with the matched normal tissues both in messenger RNA and protein level and was associated with worse prognosis. IGF2BP3 knockdown made cell cycle arrest to impair the proliferation ability of CRC cells and further inhibited the xenograft tumor growth in nude mice, also inhibited the migration ability of CRC cells via inducing epithelial-mesenchymal transition. Therefore, the research demonstrated that increased IGF2BP3 expression promoted the aggressive phenotypes of CRC cells. Targeted IGF2BP3 could be a novel and effective gene therapy for CRC patients to make a better prognosis.

Keywords: IGF2BP3; colorectal cancer; migration; prognosis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Humans
  • Male
  • Mice, Nude
  • Middle Aged
  • Multivariate Analysis
  • Phenotype
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • IGF2BP3 protein, human
  • RNA-Binding Proteins