The Roles of Non-Coding RNAs in Tumor-Associated Lymphangiogenesis

SIMPLE SUMMARY: The lymphatic system plays key roles in the bodies’ defence against disease, including cancer. The expansion of this system is termed lymphangiogenesis and it is orchestrated by factors and conditions within the microenvironment. One approach to prevent cancer progression is by interfering with these microenvironment factors that promote this process and that facilitate the spread of cancer cells to distant organs. One of these factors are non-coding RNAs. This review will summarize recent findings of the distinct roles played by non-coding RNAs in the lymphatic system within normal tissues and tumours. Understanding the mechanisms involved in this process can provide new avenues for therapeutic intervention for inhibiting the spread of cancer. ABSTRACT: Lymphatic vessels are regarded as the ”forgotten” circulation. Despite this, growing evidence has shown significant roles for the lymphatic circulation in normal and pathological conditions in humans, including cancers. The dissemination of tumor cells to other organs is often mediated by lymphatic vessels that serve as a conduit and is often referred to as tumor-associated lymphangiogenesis. Some of the most well-studied lymphangiogenic factors that govern tumor lymphangiogenesis are the vascular endothelial growth factor (VEGF-C/D and VEGFR-2/3), neuroplilin-2 (NRP2), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF), to name a few. However, recent findings have illustrated that non-coding RNAs are significantly involved in regulating gene expression in most biological processes, including lymphangiogenesis. In this review, we focus on the regulation of growth factors and non-coding RNAs (ncRNAs) in the lymphatic development in normal and cancer physiology. Then, we discuss the lymphangiogenic factors that necessitate tumor-associated lymphangiogenesis, with regards to ncRNAs in various types of cancer. Understanding the different roles of ncRNAs in regulating lymphatic vasculature in normal and cancer conditions may pave the way towards the development of ncRNA-based anti-lymphangiogenic therapy.