Exosome-based strategy against colon cancer using small interfering RNA-loaded vesicles targeting soluble a proliferation-inducing ligand

Figure 7 Mechanism of small interfering peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 RNA-loaded soluble a proliferation-inducing ligand-targeted exosomes in inhibiting epithelial-mesenchymal transition and tumor progression. Overexpression of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) leads to the downregulation of epithelial markers, such as E-cadherin and cytokeratin, and the upregulation of mesenchymal markers, including N-cadherin, Vimentin, and Snail. These changes facilitate epithelial-mesenchymal transition (EMT) through the activation of key signaling pathways involving β-catenin, Twist, small mothers against decapentaplegic 3 (Smad3), signal transducer and activator of transcription 3 (STAT3), and nuclear factor-kappa B (NF-κB), resulting in increased cell migration and invasiveness. The figure also highlights the therapeutic intervention using small interfering siPIN1 RNA (siPIN1)-loaded soluble a proliferation-inducing ligand-targeted exosomes (tEx[p]), which effectively deliver siPIN1 to tumor cells, inhibiting PIN1 activity. This targeted delivery reduces EMT, thereby decreasing tumor invasiveness and exhibiting significant antitumor effects. Arrows indicate the flow and direction of these molecular interactions and the impact of tEx[p] treatment in reversing EMT progression. sAPRIL: Soluble a proliferation-inducing ligand.