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.
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