Non-coding RNAs, such as microRNAs and long non-coding RNAs, are important regulatory molecules which are corrupted in cancer, often in a tissue and stage specific manner. Accumulated data suggests that these promising biomarkers, may also form the basis of novel targeted therapeutic strategies. The role of exosomes in cancer development and metastasis pathways is also increasingly well described. These endosome derived extracellular vesicles which are trafficked horizontally between tumor cells, and vertically between tumor cells and the surrounding microenvironment, carry bioactive cargos, which can reprogram the phenotype of recipient cells with important oncogenic consequences. Exosomes are enriched with non-coding RNA content. Within exosomes, non-coding RNAs are secreted into the peripheral circulation and other bodily fluids where they are protected from enzymatic degradation by the surrounding phospholipid membrane. Exosomes are therefore a highly promising source of diagnostic and prognostic material in cancer. Furthermore, as exosomes are natural ncRNA carriers, they may be adapted for the purpose of drug delivery by the introduction of exogenous ncRNAs or by manipulating their endogenous ncRNA content. Researchers from the University of Southampton School of Medicine explore these highly clinically relevant themes by examining the roles of exosomal ncRNAs in cancer diagnostics, prognostics and therapy.
Delivering ncRNA mimics or inhibitors to target cells via exosomes:
A putative therapeutic strategy
Exosomes derived from various cell types have been used to deliver tumor suppressor miRNAs (e.g., let-7) or oncogenic miRNA inhibitors (eg anti-miR-21) to recipient cells both in vitro and in vivo. By manipulating expression of exosome surface markers, organ specific delivery may also be achieved. The delivery of let-7a to EGFR expressing breast cancer xenografts provides the first in vivo evidence of an anticancer effect achieved with “therapeutic” ncRNAs packaged in exosomes. Abbreviations: Central Nervous System (CNS); Epidermal Growth Factor Receptor (EGFR); Spherical nanoconjugate (SNA); positive (+ve).