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. 2019 Oct 29;11(11):1681. doi: 10.3390/cancers11111681

Figure 3.

Figure 3

STAT3 response elements and STAT3 decoys. (A) The human serum-inducible element (hSIE) sequence is located upstream in the promoter region of the human c-fos gene and is almost perfectly conserved across human, feline, canine, and murine species. Sequence differences are shown in red. Below these is an optimized STAT3 binding sequence, with sequence modifications, shown in red, at positions 3 and 11 [52]. This allows the decoy to act as a direct competitive inhibitor of the DNA binding domain in the STAT3 molecule and thus inhibit expression of downstream anti-apoptotic and pro-proliferative signals. (B) Structure of the first-generation linear STAT3 decoy and mutant STAT3 decoy which is administered intratumorally in in vivo models. The location of the mutation in the mutant decoy is shown in blue. (C) Structure of the cyclic STAT3 decoy and mutant cyclic STAT3 decoy, with hexaethylene glycol linkages which is administered intravenously in in vivo models. The location of the mutation in the mutant decoy is shown in blue.