Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Angiogenesis is a rate-determining step in CRC development and metastasis. The balance of angiogenic and antiangiogenic factors is crucial in this process. Angiogenesis-related genes can be regulated post-transcriptionally by microRNAs (miRNAs) and some miRNAs have been shown to shuttle between tumor cells and the tumor microenvironment (TME). MiRNAs have context-dependent actions and can promote or suppress angiogenesis dependent on the type of cancer. On the one hand, miRNAs downregulate anti-angiogenic targets and lead to angiogenesis induction. Tumor suppressor miRNAs, on the other hand, enhance anti-angiogenic response by targeting pro-angiogenic factors. Understanding the interaction between these miRNAs and their target mRNAs will help to unravel molecular mechanisms involved in CRC progression. The aim of this article is to review the current literature on angioregulatory miRNAs in CRC.
Highlights
Angiogenesis is a coordinated multi-step process, which serves to fulfill nutrient and oxygen demand of normal and cancerous tissues and can be controlled by microRNAs at multiple levels
Endothelial cells (ECs) are a major component of the tumor microenvironment (TME) and formation of neo-vessels is critical in colorectal cancer (CRC) growth and metastasis [5]
Multiple signaling molecules and pathways such as hypoxia-inducible factor 1α (HIF1α), vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR), phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin, transforming growth factor β (TGFβ), extracellular-signal-regulated kinase (ERK) and WNT/β-catenin contribute to CRC angiogenesis
Summary
Angiogenesis is a coordinated multi-step process, which serves to fulfill nutrient and oxygen demand of normal and cancerous tissues and can be controlled by microRNAs (miRNAs) at multiple levels. Functional studies by miRNA overexpression or inhibition have revealed prominent roles of miRNAs in various types of cancer including colorectal cancer (CRC). In addition to their pivotal role in tumor cell migration and invasion, miRNAs can modulate the expression of angiogenic or anti-angiogenic factors. Exosomal angio-miRNAs and other angiogenesis-related factors released from CRC cells can transport angiogenic signals to ECs. Multiple signaling molecules and pathways such as hypoxia-inducible factor 1α (HIF1α), vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR), phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), transforming growth factor β (TGFβ), extracellular-signal-regulated kinase (ERK) and WNT/β-catenin contribute to CRC angiogenesis. We discuss the current state of research on the roles of angioregulatory miRNAs in CRC
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