Clinical utility of circulating non-coding RNAs — an update

Abstract

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.

Role of miRNAs in immune responses and immunotherapy in cancer

“…Another important aspect to be considered in the regulatory role of miRNAs in the TME is that they can exert their regulatory function also beyond the cells of origin. Indeed, in the TME, miRNAs can be transported inside extracellular vesicles (EVs) and delivered to recipient cells, regulating their biological functions . This miRNA‐mediated cell‐to‐cell communication represents an active crosstalk involving different cellular components of TME, which include cancer cells, mesenchymal stromal cells, cancer associated fibroblasts, endothelial cells, and immune cells.…”

“…Traditionally, miRNAs have been used as clinical biomarkers for cancer prognosis, diagnosis, and treatment response. 9,84 MiRNAs are powerful tumor suppressors and oncogenes with specific functions associated with cancer and have intrinsic ability to affect the efficacy of standard therapies. Moreover, as described earlier, miRNAs are also important regulators of immune cell functions and immune responses in the TME.…”

“…Therefore, the identification of patients that would have a clinical benefit from immunotherapy is instrumental to reduce unnecessary severe adverse events in patients that do not respond to these therapies. In this regard, the characterization of the TME and immune cell infiltrates can help to identify which components, such as immune cells and soluble signaling factors, are either beneficial or deleterious to patients …”

“…In this regard, the characterization of the TME and immune cell infiltrates can help to identify which components, such as immune cells and soluble signaling factors, are either beneficial or deleterious to patients. 8,9 MicroRNAs (miRNAs) are small (~21 nucleotides) endogenous noncoding RNA molecules involved in posttranscriptional regulation of gene expression. Briefly, gene expression modulation by miRNAs occurs via base pairing of the specific miRNA primary sequence to its corresponding target messenger RNA (mRNA), which can be located either in the 3' untranslated region (3'UTR) or within the coding sequence.…”

An extracellular microRNA can rescue lives in sepsis

“…In sepsis models, as well as in patients, it has been reported frequently that miRs are increased in the blood [4]. In sepsis models, as well as in patients, it has been reported frequently that miRs are increased in the blood [4].…”