Regulation of AGR2 expression via 3'UTR shortening

Exp Cell Res. 2017 Jul 1;356(1):40-47. doi: 10.1016/j.yexcr.2017.04.011. Epub 2017 Apr 11.


One recently discussed general mechanism affecting gene expression is 3'-untranslated region (3'UTR) length. Events such as shortening, translocation or loss of 3'UTRs are observed within oncogenes and are proposed to associate with increased expression. Thus, increased efforts are being made to understand constitutive and differential transcript 3'end formation. Investigation of AGR2 mRNA revealed a direct impact of its 3'UTR length on AGR2 expression. In silico analyses identified several regulatory sequences within the distal part of AGR2 mRNA that may regulate 3'UTR length and associated protein levels. Short 3'UTRs were observed in a panel of AGR2-positive cancer cell lines and in human breast cancer specimens, in which more extensive 3'UTR shortening correlated with increased AGR2 protein levels. AGR2 is an important member of PI3K/AKT signalling pathway, which along with the proposed involvement of mTOR in the regulation of alternative polyadenylation, prompted us to study the role of mTOR in relation to AGR2 mRNA 3'UTR shortening. A direct impact of mTOR signalling on AGR2 3'UTR shortening associated with increased protein synthesis was found, which led to the identification of a novel molecular mechanism involved in upregulation of AGR2 levels in mTOR-activated cells via modulating the 3'UTR length of AGR2 mRNA.

Keywords: 3’ untranslated region; 3’UTR shortening; Anterior gradient 2; mTOR.

MeSH terms

  • 3' Untranslated Regions / genetics*
  • A549 Cells
  • Breast Neoplasms / genetics
  • Cell Line, Tumor
  • Cloning, Molecular
  • Female
  • Gene Expression Regulation / genetics*
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Mechanistic Target of Rapamycin Complex 1
  • Mucoproteins
  • Multiprotein Complexes / genetics*
  • Oncogene Proteins
  • Polyadenylation / genetics
  • Protein Biosynthesis / genetics
  • Proteins / genetics*
  • Proteins / metabolism*
  • RNA, Messenger / genetics
  • Regulatory Sequences, Ribonucleic Acid / genetics
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / metabolism
  • Up-Regulation / genetics


  • 3' Untranslated Regions
  • AGR2 protein, human
  • Mucoproteins
  • Multiprotein Complexes
  • Oncogene Proteins
  • Proteins
  • RNA, Messenger
  • Regulatory Sequences, Ribonucleic Acid
  • MTOR protein, human
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases