Formation, recognition and bioactivities of a novel G-quadruplex in the STAT3 gene

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5987-91. doi: 10.1016/j.bmcl.2011.07.121. Epub 2011 Aug 6.

Abstract

G-Quadruplexes have been proved to exist in 5'-untranslated region (5'-UTR), promoter, intron and exon regions of many human genes. Here we report an intramolecular G-quadruplex formed by a G-rich sequence in the 3'-flanking region of signal transducers and activators of transcription 3 (STAT3) gene. The results showed that this G-rich sequence could affect the expression of STAT3. When the STAT3 G-quadruplex was stabilized by a novel non-planar ligand Cepharanthine (CEP), the decreased expression of STAT3 was observed in primary cultured cardiomyocytes. We also demonstrated that the down-regulation of STAT3 was most likely occurred at the transcriptional level. Our results provide a new clue for studying the G-quadruplex formation, recognition and function in the 3'-flanking region of gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Flanking Region / physiology*
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Benzylisoquinolines / chemistry
  • Benzylisoquinolines / metabolism*
  • Benzylisoquinolines / pharmacology
  • Cells, Cultured
  • Down-Regulation
  • Drug Design
  • G-Quadruplexes*
  • Gene Expression
  • Gene Expression Regulation*
  • Humans
  • Ligands
  • Luciferases / genetics
  • Luciferases / metabolism
  • Molecular Targeted Therapy*
  • Myocytes, Cardiac / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Benzylisoquinolines
  • Ligands
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • cepharanthine
  • Luciferases