Blocking the binding of WT1 to bcl-2 promoter by G-quadruplex ligand SYUIQ-FM05

• WT1 bound to double-stranded but not G-quadruplex structure in bcl-2′s promoter.
• G-quadruplexes ligand SYUIQ-FM05 blocked the binding of WT1 to bcl-2.
• SYUIQ-FM05's regulation effects depends on its interaction with GC-rich sequence.

At present, wt1, a Wilms’ tumor suppressor gene, is recognized as a critical regulator of tumorigenesis and a potential therapeutic target. WT1 shows the ability to regulate the transcription of bcl-2 by binding to a GC-rich region in the promoter, which can then fold into a special DNA secondary structure called the G-quadruplex. This function merits the exploration of the effect of a G-quadruplex ligand on the binding and subsequent regulation of WT1 on the bcl-2 promoter. In the present study, WT1 was found to bind to the double strand containing the G-quadruplex-forming sequence of the bcl-2 promoter. However, the G-quadruplex ligand SYUIQ-FM05 effectively blocked this binding by interacting with the GC-rich sequence. Our new findings are significant in the exploration of new strategies to block WT1's transcriptional regulation for cancer-cell treatment.