U1 snRNP-Dependent Suppression of Polyadenylation: Physiological Role and Therapeutic Opportunities in Cancer

Figure 3

Therapeutic potential of IPA activation: induction of secreted decoy VEGFR2. An IPA site in intron 13 of VEGFR2 can be specifically and effectively activated using ASOs targeted to the 5′ ss immediately upstream, preventing U1 from binding and thus releasing suppression [19]. This leads to the expression of a variant secreted decoy VEGFR2 encoding the sole ECD. This variant can still bind VEGF or other ligands and can still dimerize with VEGF receptors, but it cannot signal. On the contrary, it leads to a blockade of VEGF signaling in targeted and surrounding cells, with dominant negative properties.