Homo sapiens
- ISSN: 07455194
- DOI: 10.1016/S0140-6736(50)91086-5
- PubMed: 22174421
Abstract
Locally initiated RNA interference (RNAi) has the potential for spatial propagation, inducing posttranscriptional gene silencing in distant cells. In Caenorhabditis elegans, systemic RNAi (sysRNAi) requires a phylogenetically conserved transmembrane channel, SID-1. Here, we show that a human SID-1 orthologue, SIDT1, facilitates rapid, contact-dependent, bidirectional small RNA transfer between human cells, resulting in target-specific non-cell-autonomous RNAi. Intercellular small RNA transfer can both homotypic and heterotypic. We show SIDT1-mediated intercellular transfer of microRNA-21 to be a driver of resistance to the nucleoside analogue gemcitabine in human adenocarcinoma cells. Documentation of a SIDT1-dependent small RNA transfer mechanism, and the associated phenotypic effects on chemoresistance in human cancer cells, raises the possibility that conserved sysRNAi pathways contribute to the acquisition of drug resistance. Mediators of non-cell autonomous RNAi may be tractable targets for novel therapies aimed at improving the efficacy of current cytotoxic agents.
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