Exosomal miRNAs as cancer biomarkers and therapeutic targets

Abstract

Intercommunication between cancer cells and with their surrounding and distant environments is key to the survival, progression and metastasis of the tumour. Exosomes play a role in this communication process. MicroRNA (miRNA) expression is frequently dysregulated in tumour cells and can be reflected by distinct exosomal miRNA (ex-miRNA) profiles isolated from the bodily fluids of cancer patients. Here, the potential of ex-miRNA as a cancer biomarker and therapeutic target is critically analysed. Exosomes are a stable source of miRNA in bodily fluids but, despite a number of methods for exosome extraction and miRNA quantification, their suitability for diagnostics in a clinical setting is questionable. Furthermore, exosomally transferred miRNAs can alter the behaviour of recipient tumour and stromal cells to promote oncogenesis, highlighting a role in cell communication in cancer. However, our incomplete understanding of exosome biogenesis and miRNA loading mechanisms means that strategies to target exosomes or their transferred miRNAs are limited and not specific to tumour cells. Therefore, if ex-miRNA is to be employed in novel non-invasive diagnostic approaches and as a therapeutic target in cancer, two further advances are necessary: in methods to isolate and detect ex-miRNA, and a better understanding of their biogenesis and functions in tumour-cell communication.

• microRNA
• exosomes
• exosome isolation
• oncogenesis
• tumour microenvironment
• cell communication

Acknowledgements

CW gratefully acknowledges the support of the BBSRC (BB/K017462/1, BB/L007096/1), Cancer Research UK (C19591/A19076), the Cancer Research UK Oxford Centre Development Fund (C38302/A12278) and the John Fell Fund, Oxford, as well as studentships and scholarships from the Wellcome Trust, CRUK, Urology Foundation and the MRC in supporting research in this area.