Microvesicle-delivery miR-150 promotes tumorigenesis by up-regulating VEGF, and the neutralization of miR-150 attenuate tumor development

Liu, Yuchen; Zhao, Lei; Li, Dameng; Yin, Yuan; Zhang, Chenyu; Li, Jing; Zhang, Yujing

doi:10.1007/s13238-013-3092-z

Cited by 115 publications

(98 citation statements)

References 32 publications

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“…It has been described that miR-150 target up-stream proteins involved in the regulation of VEGF, thus the over-expression of this miRNA promotes the production of high levels of VEGF in experimental models of tumor development [27]. Our findings support the hypothesis that specific miRNA profiles may influence the production of pro-inflammatory mediators, these immune mediators possibly contributes with the poor regulated inflammatory phenotype characteristic of patients with severe A/H1N1 infection.…”

Section: Accepted Manuscriptsupporting

confidence: 86%

Circulating levels of miR-150 are associated with poorer outcomes of A/H1N1 infection

Morán

Ramírez-Martínez

Jiménez-Álvarez

et al. 2015

Experimental and Molecular Pathology

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Section: Accepted Manuscriptsupporting

confidence: 86%

Circulating levels of miR-150 are associated with poorer outcomes of A/H1N1 infection

Morán

Ramírez-Martínez

Jiménez-Álvarez

et al. 2015

Experimental and Molecular Pathology

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“…Many factors delivered by exosome have been found to play an important role in angiogenesis [19][20][21][22][23]43]. Endothelial cells that secrete exosomes containing miR-214 induce angiogenesis in human and mouse endothelial cells [19].…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular vesicles derived from human bone marrow mesenchymal stem cells could promote angiogenesis in tissue regeneration [17,18]. Exosomes enhance angiogenesis by delivering microRNAs, mRNAs, and active proteins [19][20][21][22][23][24]. We previously reported that exosomes from human umbilical cord mesenchymal stem cells (hucMSC-Ex) intensively enhance cutaneous wound healing; however, the effects of hucMSC-Ex on angiogenesis and the underlying mechanisms are not well characterized.…”

mentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

Zhang

et al. 2015

Stem Cells Translational Medicine

364

312

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Human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, we isolated and characterized the exosomes from hucMSCs (hucMSC-Ex) and demonstrated that hucMSC-Ex promoted the proliferation, migration, and tube formation of endothelial cells in a dose-dependent manner. Furthermore, we demonstrated that hucMSC-Ex promoted wound healing and angiogenesis in vivo by using a rat skin burn model. We discovered that hucMSC-Ex promoted b-catenin nuclear translocation and induced the increased expression of proliferating cell nuclear antigen, cyclin D3, N-cadherin, and b-catenin and the decreased expression of E-cadherin. The activation of Wnt/b-catenin is critical in the induction of angiogenesis by hucMSC-Ex, which could be reversed by b-catenin inhibitor ICG-001. Wnt4 was delivered by hucMSC-Ex, and the knockdown of Wnt4 in hucMSC-Ex abrogated b-catenin nuclear translocation in endothelial cells. The in vivo proangiogenic effects were also inhibited by interference of Wnt4 expression in hucMSC-Ex. Taken together, these results suggest that hucMSC-Ex-mediated Wnt4 induces b-catenin activation in endothelial cells and exerts proangiogenic effects, which could be an important mechanism for cutaneous wound healing. STEM CELLS TRANSLATIONAL MEDICINE 2015; 4:513-522 SIGNIFICANCEHuman umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, it is reported that hucMSC-Ex-mediated Wnt4 induces b-catenin activation in endothelial cells and exerts proangiogenic effects, which could be one of the important mechanisms responsible for cutaneous wound healing.

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“…Now, however, EVs are recognized as a genuine form of cell-cell communication that has far-reaching implications in physiological processes and disease progression (4,38,39). This has been perhaps best studied in the context of human cancer, where EVs have been linked to a number of stages of cancer progression, including the shaping of the tumor microenvironment, angiogenesis, and the creation of the premetastatic niche at secondary sites of tumor colony formation (10,40,41). The group of larger EVs, MVs, has been especially linked to changes in the tumor microenvironment, as demonstrated in studies showing that MVs isolated from the highly aggressive MDAMB231 breast cancer cell line and the U87 glioblastoma cell line caused normal (non-transformed) cell lineages to acquire the ability to grow under serum-limiting condition and survive apoptosis-inducing stresses (6).…”

Section: Discussionmentioning

confidence: 99%

Microvesicle Cargo and Function Changes upon Induction of Cellular Transformation

Kreger

Dougherty

Greene

et al. 2016

Journal of Biological Chemistry

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Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), have emerged as a major form of intercellular communication, playing important roles in several physiological processes and diseases, including cancer. EVs generated by cancer cells contain a variety of proteins and RNA species that can be transferred between cancer cells as well as between cancer and non-transformed (normal) cells, thereby impacting a number of aspects of cancer progression. Here we show how oncogenic transformation influences the biogenesis and function of EVs using a mouse embryonic fibroblast (MEF) cell line that can be induced to express an oncogenic form of diffuse B cell lymphoma (Dbl). Although MEFs induced to express oncoDbl generated a similar amount of MVs as uninduced control cells, we found that MVs isolated from onco-Dbl-transformed cells contain a unique signaling protein, the ubiquitously expressed non-receptor tyrosine kinase focal adhesion kinase. The addition of MVs isolated from MEFs expressing onco-Dbl to cultures of fibroblasts strongly promoted their survival and induced their ability to grow under anchorage-independent conditions, outcomes that could be reversed by knocking down focal adhesion kinase and depleting it from the MVs or by inhibiting its kinase activity using a specific inhibitor. We then showed the same to be true for MVs isolated from aggressive MDAMB231 breast cancer cells. Together, these findings demonstrate that the induction of oncogenic transformation gives rise to MVs, which uniquely contain a signaling protein kinase that helps propagate the transformed phenotype and thus may offer a specific diagnostic marker of malignant disease.Classical intercellular signaling involves the secretion of growth factors, pro-inflammatory cytokines, and extracellular matrix proteins by a cell into its local environment (1, 2). These soluble factors then bind to their corresponding receptors expressed in a neighboring cell and induce the activation of intracellular signaling events that determine whether a cell grows, differentiates, migrates, or dies (3). These types of paracrine signaling activities are required throughout development and for tissue homeostasis, whereas deregulation of these events often leads to developmental abnormalities and the onset of diseases.The generation of EVs 3 by cells has quickly become appreciated as another major form of intercellular communication with important consequences in biology (4 -7). Cells generate two distinct types of EVs: MVs and exosomes. MVs typically range in size from 0.2-2.0 m in diameter and are formed via the budding and release (shedding) of membrane-enclosed packages from plasma membranes. Exosomes represent the second major class of EVs. They are significantly smaller than MVs, averaging only 0.03-0

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Microvesicle-delivery miR-150 promotes tumorigenesis by up-regulating VEGF, and the neutralization of miR-150 attenuate tumor development

Cited by 115 publications

References 32 publications

Circulating levels of miR-150 are associated with poorer outcomes of A/H1N1 infection

Circulating levels of miR-150 are associated with poorer outcomes of A/H1N1 infection

Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

Microvesicle Cargo and Function Changes upon Induction of Cellular Transformation

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