microRNA-mediated regulation of the tumor microenvironment

Abstract

The tumor microenvironment includes cells such as fibroblasts, immune cells, endothelial cells, as well as extracellular matrix (ECM), proteases, and cytokines. Together, these components participate in a complex crosstalk with neoplastic tumor cells that affects growth, angiogenesis, and metastasis. MicroRNAs (miRNAs) are small, non-coding RNAs involved in post-transcriptional regulation of gene expression and have recently emerged as important players involved in regulating multiple aspects of cancer biology and the tumor microenvironment. Differential miRNA expression in both the epithelial and stromal compartments of tumors compared with normal tissue suggests that miRNAs are important drivers of tumorigenesis and metastasis. This review article summarizes our current understanding of the diverse roles of miRNAs involved in tumor microenvironment regulation and underscores the importance of miRNAs within multiple cell types that contribute to the hallmarks of cancer.

Figure 1. microRNA-mediated control of the tumor microenvironment. The tumor microenvironment is shown, which is composed of cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), endothelial cells, and immune cells (such as T cells and macrophages). Cytokines produced by various cell types recruit other bone-marrow derived and immune cells into the vicinity. Matrix metalloproteinases (MMPs) cleave the ECM and also release sequestered growth factors. Many cell types within the microenvironment and biological processes that contribute to tumor growth (such as angiogenesis, the hypoxic response, and collagen remodeling) are subject to miRNA regulation.