miRNAs as Influencers of Cell-Cell Communication in Tumor Microenvironment

Abstract

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level, inducing the degradation of the target mRNA or translational repression. MiRNAs are involved in the control of a multiplicity of biological processes, and their absence or altered expression has been associated with a variety of human diseases, including cancer. Recently, extracellular miRNAs (ECmiRNAs) have been described as mediators of intercellular communication in multiple contexts, including tumor microenvironment. Cancer cells cooperate with stromal cells and elements of the extracellular matrix (ECM) to establish a comfortable niche to grow, to evade the immune system, and to expand. Within the tumor microenvironment, cells release ECmiRNAs and other factors in order to influence and hijack the physiological processes of surrounding cells, fostering tumor progression. Here, we discuss the role of miRNAs in the pathogenesis of multicomplex diseases, such as Alzheimer's disease, obesity, and cancer, focusing on the contribution of both intracellular miRNAs, and of released ECmiRNAs in the establishment and development of cancer niche. We also review growing evidence suggesting the use of miRNAs as novel targets or potential tools for therapeutic applications.

Keywords: cancer therapy; cell–cell communication; extracellular miRNA; microRNA; tumor microenvironment.

Figure 1

Cell–cell communication within the tumor microenvironment: On the left, factors and ECmiRNAs released by cells or extracellular matrix toward cancer cells; on the right, factors and ECmiRNAs released by cancer cells that stimulate biological pathways in recipient cells. ↑ Upregulation; ↓ Downregulation; ASC: Adipose-derived Stem Cell; DC: Dendritic Cell; ECM: Extracellular Matrix; LPA: Lysophosphatidic Acid; MDSC: Myeloid-derived suppressor cell; NK: Natural Killer cell.