MicroRNAs and angiogenesis: a new era for the management of colorectal cancer

Abstract

MicroRNAs (miRNAs) are a class of small noncoding RNA molecules containing only 20–22 nucleotides. MiRNAs play a role in gene silencing and translation suppression by targeting and binding to mRNA. Proper control of miRNA expression is very important for maintaining a normal physiological environment because miRNAs can affect most cellular pathways, including cell cycle checkpoint, cell proliferation, and apoptosis pathways, and have a wide range of target genes. With these properties, miRNAs can modulate multiple signalling pathways involved in cancer development, such as cell proliferation, apoptosis, and migration pathways. MiRNAs that activate or inhibit the molecular pathway related to tumour angiogenesis are common topics of research. Angiogenesis promotes tumorigenesis and metastasis by providing oxygen and diffusible nutrients and releasing proangiogenic factors and is one of the hallmarks of tumour progression. CRC is one of the most common tumours, and metastasis has always been a difficult issue in its treatment. Although comprehensive treatments, such as surgery, radiotherapy, chemotherapy, and targeted therapy, have prolonged the survival of CRC patients, the overall response is not optimistic. Therefore, there is an urgent need to find new therapeutic targets to improve CRC treatment. In a series of recent reports, miRNAs have been shown to bidirectionally regulate angiogenesis in colorectal cancer. Many miRNAs can directly act on VEGF or inhibit angiogenesis through other pathways (HIF-1a, PI3K/AKT, etc.), while some miRNAs, specifically many exosomal miRNAs, are capable of promoting CRC angiogenesis. Understanding the mechanism of action of miRNAs in angiogenesis is of great significance for finding new targets for the treatment of tumour angiogenesis. Deciphering the exact role of specific miRNAs in angiogenesis is a challenge due to the high complexity of their actions. Here, we describe the latest advances in the understanding of miRNAs and their corresponding targets that play a role in CRC angiogenesis and discuss possible miRNA-based therapeutic strategies.

Relationship between VEGF Family Members, Their Receptors and Cell Death in the Neoplastic Transformation of Colorectal Cancer

“…Mainly, when a tumor is more than 2 mm in diameter, it cannot grow further based on tissue penetration due to a hypoxic microenvironment of the tumor. Hence the tumor needs the formation of new blood vessels to supply oxygen and nutrients [ 36 ]. New vasculature is shaped in and around the tumor to allow it to grow exponentially.…”

“…Tumor hypoxia usually occurs during the anti-angiogenic period and is suspected to play a significant role in anti-angiogenic drug resistance [ 48 ]. Nevertheless, the long-term use of bevacizumab has some side effects, e.g., osteonecrosis [ 36 ].…”

The role of pro- and antiangiogenic factors in angiogenesis process by Raman spectroscopy

“…14 15 Deregulation of the balance between above-mentioned factors causes pathologic conditions such as cancer development. 16 17 This hypothesis for the first time was described by Folkman. 18 Growing tumor cannot live without oxygen and nutrient.…”

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

“…Additionally, a recent review cites studies that identified miR-1249, miR-126, miR-27b, 520a, miR-590-5p and miR-622 as inhibitors of angiogenesis in colorectal cancer (CRC). These miRNAs inhibit vascular endothelial growth factor A, whose elevated levels are closely related to CRC invasion and metastasis, through different pathways [259].…”