Tumor necrosis factor alpha delivers exogenous inflammation-related microRNAs to recipient cells with functional targeting capabilities

Tumor necrosis factor alpha (TNF-a) is a critical pro -inflam-matory cytokine in a wide range of tumors and infectious dis-eases. This study showed for the first time that TNF-a could specifically bind to certain intracellular or circulating inflam-mation-related microRNAs both in vitro and in vivo. The bind-ing sites of TNF-a to microRNAs are located at the N-terminal of TNF-a and the 30-GGUU motif of microRNAs. TNF-a could deliver exogenous unmodified single-stranded microRNAs into recipient cells through the TNF-a receptors (TNFRs) and stabilize them from being degraded by RNase in cells. Exogenous miR-146a or let-7c delivered into HCT116 cells by TNF-a could escape from lysosomes and specifically downregu-late their target genes and then affect cell proliferation and migration in vitro, as well as tumorigenesis in vivo. Based on the above findings, the concept of non-conjugated ligand-mediated RNA delivery (ncLMRD) was proposed, which may serve as a promising strategy for therapeutic microRNA delivery in the future.

Automated summary

This study demonstrates the specific binding of TNF-a to certain inflammation-related microRNAs and its delivery into recipient cells through TNF-a receptors, highlighting the potential of TNF-a as a delivery system for therapeutic microRNAs.