Inhibitory DNA Aptamer Tools against SOCS3-gp130 Interactions

Abstract

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway plays a crucial role in transmembrane signal transduction, enabling cells to communicate with the extracellular environment, which requires precise regulation to prevent abnormal signaling outcomes. Within this complex pathway, suppressor of cytokine signaling 3 (SOCS3) acts as a pivotal negative regulator via binding to cytokine receptors. However, our understanding of the regulatory mechanisms governing SOCS3 interactions has been limited by the lack of suitable chemical probes. Aptamers, a notable category of chemical tools, have emerged as a viable avenue for the development of chemical inhibitors. In this study, we successfully identified specific inhibitory aptamers that bind to SOCS3 and effectively disrupt the interaction between SOCS3 and glycoprotein 130, a common cytokine receptor for interleukin-6 and leukemia inhibitory factor, which regulates the survival of normal human endometrial stromal cells. These aptamers not only provide a valuable chemical tool to advance our understanding of the regulatory dynamics of the JAK/STAT signaling pathway by SOCS3 but also hold great promise for the future development of therapeutic interventions.