Clinical utility of circulating non-coding RNAs - an update

Over the past decade, the amount of research and the number of publications on associations between circulating small and long non-coding RNAs (ncRNAs) and cancer have grown exponentially. Particular focus has been placed on the development of diagnostic and prognostic biomarkers to enable efficient patient management-from early detection of cancer to monitoring for disease recurrence or progression after treatment. Owing to their high abundance and stability, circulating ncRNAs have potential utility as non-invasive, blood-based biomarkers that can provide information on tumour biology and the effects of treatments, such as targeted therapies and immunotherapies. Increasing evidence highlights the roles of ncRNAs in cell-to-cell communication, with a number of ncRNAs having the capacity to regulate gene expression outside of the cell of origin through extracellular vesicle-mediated transfer to recipient cells, with implications for cancer progression and therapy resistance. Moreover, 'foreign' microRNAs (miRNAs) encoded by non-human genomes (so-called xeno-miRNAs), such as viral miRNAs, have been shown to be present in human body fluids and can be used as biomarkers. Herein, we review the latest developments in the use of circulating ncRNAs as diagnostic and prognostic biomarkers and discuss their roles in cell-to-cell communication in the context of cancer. We provide a compendium of miRNAs and long ncRNAs that have been reported in the literature to be present in human body fluids and that have the potential to be used as diagnostic and prognostic cancer biomarkers.