The RNA Binding Protein IMP2 Preserves Glioblastoma Stem Cells by Preventing let-7 Target Gene Silencing

Cell Rep. 2016 May 24;15(8):1634-47. doi: 10.1016/j.celrep.2016.04.086. Epub 2016 May 12.


Cancer stem cells (CSCs) can drive tumor growth, and their maintenance may rely on post-transcriptional regulation of gene expression, including that mediated by microRNAs (miRNAs). The let-7 miRNA family has been shown to induce differentiation by silencing stem cell programs. Let-7-mediated target gene suppression is prevented by LIN28A/B, which reduce let-7 biogenesis in normal embryonic and some cancer stem cells and ensure maintenance of stemness. Here, we find that glioblastoma stem cells (GSCs) lack LIN28 and express both let-7 and their target genes, suggesting LIN28-independent protection from let-7 silencing. Using photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we show that insulin-like growth factor 2 mRNA-binding protein 2 (IMP2) binds to let-7 miRNA recognition elements (MREs) and prevents let-7 target gene silencing. Our observations define the RNA-binding repertoire of IMP2 and identify a mechanism whereby it supports GSC and neural stem cell specification.

MeSH terms

  • Base Sequence
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Adhesion
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Neural Stem Cells / metabolism
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Spheroids, Cellular / pathology


  • IGF2BP2 protein, human
  • LIN28B protein, human
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
  • mirnlet7 microRNA, human