Figure 1.

Crosstalk of circulating non-coding RNAs and tumor microenvironment. (A) The tumor microenvironment (TME) includes a cellular and an extracellular component. The cellular component consists of tumor cells, immune cells (TAMs, T cells, B cells, NK cells, DCs, and MDSCs) and cancer-associated fibroblasts (CAFs). The extracellular component of TME is composed by ECM proteins and signaling molecules (like cytokines, chemokines, growth factors, hormones, etc.), which are secreted by the cellular component. (B) ncRNAs are processed and released in body fluids. Circulating ncRNAs can be released in two ways: (1) as cell-free RNAs, complexed with protein such as AGO, NPM1 or HDL; or (2) in extracellular vesicles (exosomes and microvesicles). Both tumor cells and stromal cells may release exosomes in the TME. Through body fluids, ncRNAs can reach distant sites in the body and act as molecular mediators. (C) Circulating ncRNAs are stable and easily detectable and can be used as non-invasive biomarkers in liquid biopsy. TME: tumor microenvironment, TAM: Tumor-associated macrophage, NK: Natural killer cell, DC: Dendritic cell, MDSC: Myeloid-derived suppressor cell, CAF: cancer-associated fibroblast, ECM: extracellular matrix, SDE: Stromal-derived exosome, CDE: Cancer-derived exosome, AGO: Argonaute2, NPM1: Nucleophosmin 1, HDL: High-density lipoprotein, MVB: Multivesicular body, MV: Microvesicle, CTC: Circulating tumor cell.