miR-181a, delivered by hypoxic PTC-secreted exosomes, inhibits DACT2 by downregulating MLL3, leading to YAP-VEGF-mediated angiogenesis

Wang, Yingxue; Cen, A; Yang, Yuxian; Ye, Huilin; Li, Jiaying; Liu, Shiliang; Zhao, Lei

doi:10.1016/j.omtn.2021.02.027

Cited by 32 publications

(21 citation statements)

References 50 publications

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“…In papillary thyroid cancer, hypoxia promoted both the expression of miR-181a in cancer cells and the secretion of miR-181a enriched exosomes from cancer cells. Human umbilical vein endothelial cells (HUVECs) which uptake such exosomes exhibited enhanced proliferation and capillary-like network formation, contributing to tumor angiogenesis ( 117 ). In skin carcinoma A431 cells, hypoxia induced the expression of proteins involved in angiogenesis, focal adhesion, extracellular matrix-receptor interaction, and immune cell recruitment.…”

Section: Hypoxic Exosomes Promote the Development Of Different Types ...mentioning

confidence: 99%

Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects

et al. 2022

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Exosomes are small extracellular vesicles that are secreted by almost all types of cells and exist in almost all extracellular spaces. As an important mediator of intercellular communication, exosomes encapsulate the miRNA, lncRNA, cirRNA, mRNA, cytokine, enzyme, lipid, and other components from the cytoplasm into its closed single membrane structure and transfer them to recipient units in an autocrine, paracrine, or endocrine manner. Hypoxia is a state of low oxygen tension and is involved in many pathological processes. Hypoxia influences the size, quantity, and expression of exosome cargos. Exosomes derived from hypoxic tumor cells transfer genetics, proteins, and lipids to the recipient units to exert pleiotropic effects. Different donor cells produce different cargo contents, target different recipient units and lead to different biological effects. Hypoxic exosomes derived from tumor cells uptaken by normoxic tumor cells lead to promoted proliferation, migration, and invasion; uptaken by extracellular space or liver lead to promoted metastasis; uptaken by endothelial cells lead to promoted angiogenesis; uptaken by immune cells lead to promoted macrophage polarization and changed tumor immune microenvironment. In addition to various types of tumors, hypoxic exosomes also participate in the development of diseases in the cardiovascular system, neuron system, respiratory system, hematology system, endocrine system, urinary system, reproduction system, and skeletomuscular system. Understanding the special characteristics of hypoxic exosomes provide new insight into elaborating the pathogenesis of hypoxia related disease. This review summarizes hypoxia induced cargo changes and the biological effects of hypoxic exosomes in tumors and non-malignant diseases in different systems.

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Section: Hypoxic Exosomes Promote the Development Of Different Types ...mentioning

confidence: 99%

Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects

et al. 2022

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“…Depending on the cargo of exosomes, they can act as tumor suppressive or tumor promoting factors to influence angiogenesis in cancer cells. Exosomes can affect various molecular signaling pathways such as MAPK, YAP, VEGF, and miRNAs in modulating angiogenesis in cancer cells (Table 1) [136][137][138][139][140][141]. Figure 3 illustrates the role of exosomes in regulating angiogenesis in cancer cells.…”

Section: Exosomes and Tumor Angiogenesismentioning

confidence: 99%

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

et al. 2022

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Cancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment. Graphical Abstract

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“…It is caused by the rapid tumor growth that runs out the supply of oxygen, and impairment of blood flow results from the aberrant blood vessels in the tumor (66). It can promote angiogenesis and tumor progression via altering the tumor microenvironment (TME) (67,68). In a recent study by Li et al, hypoxic GBMsecreted miR-182-5p could be taken up by human umbilical vein ECs (HUVECs) via exosomes, which could promote angiogenesis by directly suppressing Kruppel-like Factor 2 and 4 (KLF2 and KLF4) and subsequently elevating VEGF receptors (VEGFR) expression (36).…”

Section: Exosomal Mirnas and Angiogenesis In Gliomamentioning

confidence: 99%

Current Understanding of Exosomal MicroRNAs in Glioma Immune Regulation and Therapeutic Responses

Peng

Liang

et al. 2022

Front. Immunol.

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Exosomes, the small extracellular vesicles, are released by multiple cell types, including tumor cells, and represent a novel avenue for intercellular communication via transferring diverse biomolecules. Recently, microRNAs (miRNAs) were demonstrated to be enclosed in exosomes and therefore was protected from degradation. Such exosomal miRNAs can be transmitted to recipient cells where they could regulate multiple cancer-associated biological processes. Accumulative evidence suggests that exosomal miRNAs serve essential roles in modifying the glioma immune microenvironment and potentially affecting the malignant behaviors and therapeutic responses. As exosomal miRNAs are detectable in almost all kinds of biofluids and correlated with clinicopathological characteristics of glioma, they might be served as promising biomarkers for gliomas. We reviewed the novel findings regarding the biological functions of exosomal miRNAs during glioma pathogenesis and immune regulation. Furthermore, we elaborated on their potential clinical applications as biomarkers in glioma diagnosis, prognosis and treatment response prediction. Finally, we summarized the accessible databases that can be employed for exosome-associated miRNAs identification and functional exploration of cancers, including glioma.

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miR-181a, delivered by hypoxic PTC-secreted exosomes, inhibits DACT2 by downregulating MLL3, leading to YAP-VEGF-mediated angiogenesis

Cited by 32 publications

References 50 publications

Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects

Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

Current Understanding of Exosomal MicroRNAs in Glioma Immune Regulation and Therapeutic Responses

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