Noncoding RNAs in tumor angiogenesis

Abstract

Solid tumors require angiogenesis to grow beyond 2 mm in size. In most cases, tumor cells undergo angiogenic switch and secrete substances that are required for generation of new capillary sprouting from existing blood vessels. Tumor angiogenesis is driven by a complex interplay between pro-angiogenic (VEGF/VEGFR, PDGF/PDGFR) and anti-angiogenic factors (TSP-1/TSP-2) within the tumor microenvironment. In addition, control of tissue remodeling and degradation by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) contribute to tumor angiogenesis. Furthermore, tumor suppressors or oncogenes that control cellular motility and maintain or promote hypoxia (HIFs and MYC) are also actively playing roles in tumor angiogenesis. Noncoding RNAs (ncRNAs), including microRNAs, are a novel class of regulatory molecules that control the gene expression in a posttranscriptional manner. MicroRNAs regulate important physiological processes, such as proliferation, apoptosis, and differentiation, as well as pathological conditions including oncogenesis. Accumulating evidence suggests that microRNAs directly modulate the process of angiogenesis by targeting important angiogenic factors and signaling molecules. Understanding the molecular mechanism behind the regulation of angiogenesis by microRNAs is important due to their therapeutic potential which may lead to improving outcome for cancer patients. Besides, ncRNAs with a regulatory role in angiogenesis, such as long noncoding RNAs (lncRNAs), have been identifi ed in the genome. However, the mechanisms of the vast majority of lncRNAs are currently unknown. For the few lncRNAs characterized at the functional level, accumulating evidence shows that they play important roles in malignant diseases. The function and mechanism in angiogenesis will be described in this chapter.