Abstract
Tumour angiogenesis and lymphangiogenesis are hallmarks of cancer and have been associated with tumour progression, tumour metastasis and poor patient prognosis. Many factors regulate angiogenesis and lymphangiogenesis in cancer including non-coding RNAs which are a category of RNAs that do not encode proteins and have important regulatory functions at transcriptional and post-transcriptional levels. Non-coding RNAs can be encapsulated in extracellular vesicles called exosomes which are secreted by tumour cells or other cells in the tumour microenvironment and can then be taken up by the endothelial cells of blood vessels and lymphatic vessels. The “delivery” of these non-coding RNAs to endothelial cells in tumours can facilitate tumour angiogenesis and lymphangiogenesis. Here we review recent findings about exosomal non-coding RNAs, specifically microRNAs and long non-coding RNAs, which regulate tumour angiogenesis and lymphangiogenesis in cancer. We then focus on the potential use of these molecules as cancer biomarkers and opportunities for exploiting ncRNAs for the treatment of cancer.
Highlights
The growth of new tumour blood vessels and lymphatic vessels is a key element of cancer progression having a close association with metastatic spread, poor patient prognosis and survival [1,2]
Nuclear miRNAs play a role in transcription by recruiting transcriptional activator and repressor chromatin remodelling proteins [6], and miRNAs are involved in the post-transcriptional regulation of mRNAs by modulating their translation or degradation, e.g., miR-29-b inhibits angiogenesis by negatively regulating the expression of vascular endothelial growth factor A (VEGFA) and Akt3 [11,12]. Long ncRNAs (lncRNAs) can act post-transcriptionally to regulate mRNA by modulating mRNA splicing, translation and mRNA degradation, e.g., lncRNA MALAT1 plays a role in angiogenesis through several mechanisms including the regulation of alternative splicing of the oncogenic transcription factor B-MYB in endothelial cells [13], WTAPP1 lncRNA promotes migration by increasing the expression of the matrix metalloproteinase MMP1 [14] and Tie-1AS lncRNA
We summarise recent discoveries about ncRNAs, both miRNAs and lncRNAs, which are secreted by cancer cells in exosomes and which facilitate tumour angiogenesis and lymphangiogenesis
Summary
The growth of new tumour blood vessels and lymphatic vessels is a key element of cancer progression having a close association with metastatic spread, poor patient prognosis and survival [1,2]. Nuclear miRNAs play a role in transcription by recruiting transcriptional activator and repressor chromatin remodelling proteins [6], and miRNAs are involved in the post-transcriptional regulation of mRNAs by modulating their translation or degradation, e.g., miR-29-b inhibits angiogenesis by negatively regulating the expression of VEGFA and Akt3 [11,12]. An important functional feature of miRNAs and lncRNAs is that they can exert effects on the regulation of complex biological responses: miRNAs by targeting mRNAs encoding multiple proteins involved in the same or a related molecular pathway, lncRNAs by controlling the remodelling of chromatin to modulate gene expression, or by targeting miRNAs. a miRNA can act in concert with other miRNAs, lncRNAs or transcription factors to mediate gene silencing in a precise manner. We discuss the use of these tumour-derived exosomal ncRNAs as tumour biomarkers, and the potential of exploiting ncRNAs for treating cancer
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