miR-1275: A single microRNA that targets the three IGF2-mRNA-binding proteins hindering tumor growth in hepatocellular carcinoma

FEBS Lett. 2015 Aug 4;589(17):2257-65. doi: 10.1016/j.febslet.2015.06.038. Epub 2015 Jul 6.

Abstract

This study aimed to identify a single miRNA or miR (microRNA) which regulates the three insulin-like growth factor-2-mRNA-binding proteins (IGF2BP1, 2 and 3). Bioinformatics predicted miR-1275 to simultaneously target the three IGF2BPs, and screening revealed miR-1275 to be underexpressed in hepatocellular carcinoma (HCC) tissues. Transfection of HuH-7 cells with miR-1275 suppressed IGF2BPs expression and all three IGF2BPs were confirmed as targets of miR-1275. Ectopic expression of miR-1275 and knockdown of IGF2BPs inhibited malignant cell behaviors, and also reduced IGF1R protein and mRNA. Finally IGF1R was validated as a direct target of miR-1275. These findings indicate that the tumor-suppressor miR-1275 can control HCC tumor growth partially through simultaneously regulating the oncogenic IGF2BPs and IGF1R.

Keywords: Hepatocellular carcinoma; Insulin-like growth factor 1 receptor (IGF1R); Insulin-like growth factor-2-mRNA-binding protein (IGF2BP or IMP); Posttranscriptional regulation; miR-1275; miRNA or miR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / genetics
  • Receptors, Somatomedin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Tumor Burden / genetics
  • Young Adult

Substances

  • 3' Untranslated Regions
  • IGF1R protein, human
  • IGF2BP1 protein, human
  • IGF2BP2 protein, human
  • IGF2BP3 protein, human
  • MIRN1275 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, Somatomedin
  • Receptor, IGF Type 1