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Review
. 2022 Mar 10;11(6):947.
doi: 10.3390/cells11060947.

Noncoding RNAs of Extracellular Vesicles in Tumor Angiogenesis: From Biological Functions to Clinical Significance

Miao Hu  1 , Juan Li  2 , Chen-Guang Liu  1 , Robby Miguel W J Goh  3 , Fenggang Yu  4 , Zhaowu Ma  1 , Lingzhi Wang  5   6   7
Affiliations
Review

Noncoding RNAs of Extracellular Vesicles in Tumor Angiogenesis: From Biological Functions to Clinical Significance

Miao Hu et al. Cells. .

Abstract

Extracellular vesicles (EVs) act as multifunctional regulators of intercellular communication and are involved in diverse tumor phenotypes, including tumor angiogenesis, which is a highly regulated multi-step process for the formation of new blood vessels that contribute to tumor proliferation. EVs induce malignant transformation of distinct cells by transferring DNAs, proteins, lipids, and RNAs, including noncoding RNAs (ncRNAs). However, the functional relevance of EV-derived ncRNAs in tumor angiogenesis remains to be elucidated. In this review, we summarized current research progress on the biological functions and underlying mechanisms of EV-derived ncRNAs in tumor angiogenesis in various cancers. In addition, we comprehensively discussed the potential applications of EV-derived ncRNAs as cancer biomarkers and novel therapeutic targets to tailor anti-angiogenic therapy.

Keywords: cancer biomarkers; drug resistance; extracellular vesicles; noncoding RNAs; tumor angiogenesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Formation and release of EVs. The formation of EVs involves the following processes: Proteins are transported from the Golgi apparatus or internalised from the cell surface, and nucleic acids are endocytosed and transferred to early endosomes. Early endosomes gradually mature into late endosomes and MVBs, some of which are degraded, whereas others are secreted as exosomes. These exosomes carry multiple biological components, including proteins, lipids, and nucleic acids (e.g., ncRNAs), which are delivered to the recipient cell through different ways: a. phagocytosis, b. receptor–ligand interaction, and c. direct fusion.
Figure 2
Figure 2
EV-derived ncRNAs regulate cell–cell communication in the angiogenic microenvironment. Tumor cells (A), immune cells, and stromal cells (B) release EVs containing miRNAs, lncRNAs, circRNAs, and piRNAs, contributing to tumor angiogenesis within the tumor microenvironment. ECs: endothelial cells, CAFs: cancer-associated fibroblasts, and MSCs: mesenchymal stromal cells.
Figure 3
Figure 3
The potential clinical application of EV-derived ncRNAs in tumor angiogenesis (A) EV-derived ncRNAs can be detected from patient samples and are potential diagnostic and prognostic biomarkers. (B) A combination of targeting EV-derived ncRNAs and using conventional anti-angiogenic agents can enhance therapeutic efficacy.
See this image and copyright information in PMC

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