Chasing the Role of miRNAs in RCC: From Free-Circulating to Extracellular-Vesicle-Derived Biomarkers

Abstract

Renal cell carcinoma (RCC) is the second most common cancer of the urinary system. The current therapeutic strategies are based on partial or total nephrectomy and/or targeted therapies based on immune checkpoint inhibitors to which patients are often refractory. Preventive and screening strategies do not exist and the few available biomarkers for RCC are characterized by a lack of sensitivity, outlining the need for novel noninvasive and sensitive biomarkers for early diagnosis and better disease monitoring. Blood liquid biopsy (LB) is a non- or minimally invasive procedure for a more representative view of tumor heterogeneity than a tissue biopsy, potentially allowing the real-time monitoring of cancer evolution. Growing interest is focused on the extracellular vesicles (EVs) secreted by either healthy or tumoral cells and recovered in a variety of biological matrices, blood included. EVs are involved in cell-to-cell crosstalk transferring their mRNAs, microRNAs (miRNAs), and protein content. In particular, transferred miRNAs may regulate tumorigenesis and proliferation also impacting resistance to apoptosis, thus representing potential useful biomarkers. Here, we present the latest efforts in the identification of circulating miRNAs in blood samples, focusing on the potential use of EV-derived miRNAs as RCC diagnostic and prognostic markers.

Extracellular Vesicles in Kidney Disease

“…With the pivotal roles in an exchange between renal cells and target cells, EVs are expected to serve as new molecular markers for the detection of kidney diseases, carrying specific molecular substances in source renal cells with the lipid structure to protect the contents from being degraded [48,49]. At present, the study of EVs, especially exosomes, has been involved in the field of liquid biopsy [50,51].…”

Macrophage-derived ectosomal miR-350-3p promotes osteoarthritis progression through downregulating chondrocyte H3K36 methyltransferase NSD1

“…Furthermore, synovial fibroblasts delivered microRNAs(miRNAs) to chondrocytes through EVs to mediate chondrocyte function, indicating that the EVs delivery function may be a potential mechanism in OA progression [ 18 ]. According to their different modes of biogenesis and release, EVs can be divided into exosomes (diameter 30–150 nm, formed through inward budding of the endosomal membrane), ectosomes (diameter 100–1000 nm, originated from the plasma membrane through outward budding), and apoptotic bodies (derived from terminal apoptotic cells) [ 19 – 21 ]. In recent years, with the expanding research on EVs subtypes, it has been found that the biochemistry and functions of ectosomes and exosomes were distinct [ 22 – 24 ].…”