Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect

Xu, Shuai; Wang, Jufang; Ding, Nan; Hu, Wentao; Zhang, Xurui; Wang, Bing; Hua, Junrui; Wei, Wenjun; Zhu, Qing

doi:10.1080/15476286.2015.1100795

Cited by 146 publications

(123 citation statements)

References 44 publications

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“…Irradiation of a given cell can trigger the upregulation of specific miRNAs such as those involved in DNA damage response functions [32]. Through packaging of these miRNAs within vesicles such as exosomes, the miRNAs are easily exchanged intercelluarly and can subsequently elicit bystander effects in recipient cells.…”

Section: Discussionmentioning

confidence: 99%

Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect

Fernández-Palomo

McNeill

et al. 2017

PLoS ONE

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ObjectiveThe objective of our study was to explore a possible molecular mechanism by which ultraviolet (UV) biophotons could elicit bystander responses in reporter cells and resolve the problem of seemingly mutually exclusive mechanisms of a physical UV signal & a soluble factor-mediated bystander signal.MethodsThe human colon carcinoma cell line, HCT116 p53 +/+, was directly irradiated with 0.5 Gy tritium beta particles to induce ultraviolet biophoton emission. Bystander cells were not directly irradiated but were exposed to the emitted UV biophotons. Medium was subsequently harvested from UV-exposed bystander cells. The exosomes extracted from this medium were incubated with reporter cell populations. These reporter cells were then assayed for clonogenic survival and mitochondrial membrane potential with and without prior treatment of the exosomes with RNase.ResultsClonogenic cell survival was significantly reduced in reporter cells incubated with exosomes extracted from cells exposed to secondarily-emitted UV. These exosomes also induced significant mitochondrial membrane depolarization in receiving reporter cells. Conversely, exosomes extracted from non-UV-exposed cells did not produce bystander effects in reporter cells. The treatment of exosomes with RNase prior to their incubation with reporter cells effectively abolished bystander effects in reporter cells and this suggests a role for RNA in mediating the bystander response elicited by UV biophotons and their produced exosomes.ConclusionThis study supports a role for exosomes released from UV biophoton-exposed bystander cells in eliciting bystander responses and also indicates a reconciliation between the UV-mediated bystander effect and the bystander effect which has been suggested in the literature to be mediated by soluble factors.

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Section: Discussionmentioning

confidence: 99%

Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect

Fernández-Palomo

McNeill

et al. 2017

PLoS ONE

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“…A large number of studies have raised that the extracellular miRNAs may play an important role in regulating intercellular communication and thus have implications in tumor biology [13, 16, 29, 30, 36]. In addition, some evidences indicate that extracellular miRNAs are relevant to RIBE [24, 25]. However, there is no literature concerning the role of radiation-induced extracellular miRNAs in regulating cell radiosensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have confirmed that many kinds of diffusible signaling factors contribute to the generation of RIBE, including reactive oxygen species (ROS), reactive nitrogen species (RNS), cytochrome-c and cytokines [21–23]. Recently, it was reported that miR-663 and miR-21 were involved in the RIBE through a medium-mediated pathway [24, 25]. However, the characteristics of extracellular miRNA expressions responding to IR and the potential roles of miRNAs in regulating cell radiosensitivity are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Extracellular miR-1246 promotes lung cancer cell proliferation and enhances radioresistance by directly targeting DR5

Yuan

Wang

et al. 2016

Oncotarget

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MiRNAs in the circulation have been demonstrated to be a type of signaling molecule involved in intercellular communication but little is known about their role in regulating radiosensitivity. This study aims to investigate the effects of extracellular miRNAs induced by ionizing radiation (IR) on cell proliferation and radiosensitivity. The miRNAs in the conditioned medium (CM) from irradiated and non-irradiated A549 lung cancer cells were compared using a microarray assay and the profiles of 21 miRNAs up and down-regulated by radiation were confirmed by qRT-PCR. One of these miRNAs, miR-1246, was especially abundant outside the cells and had a much higher level compared with that inside of cells. The expressions of miR-1246 in both A549 and H446 cells increased along with irradiation dose and the time post-irradiation. By labeling exosomes and miR-1246 with different fluorescence dyes, it was found that the extracellular miR-1246 could shuttle from its donor cells to other recipient cells by a non-exosome associated pathway. Moreover, the treatments of cells with miR-1246 mimic or its antisense inhibitor showed that the extracellular miR-1246 could enhance the proliferation and radioresistance of lung cancer cells. A luciferase reporter-gene transfer experiment demonstrated that the death receptor 5 (DR5) was the direct target of miR-1246, and the kinetics of DR5 expression was opposite to that of miR-1246 in the irradiated cells. Our results show that the oncogene-like extracellular miR-1246 could act as a signaling messenger between irradiated and non-irradiated cells, more importantly, it contributes to cell radioresistance by directly suppressing the DR5 gene.

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“…Interestingly, transfection of miR-21 mimics into MRC-5 cells induced similar effects, suggesting a role for miR-21 in mediating RIBE. In a follow-up study, the same group demonstrated that exosomes isolated from irradiated CM could induce bystander effects by mediating miR-21 transfer from irradiated to bystander cells (149). Inhibition of miR-21 before irradiation blunted these effects, suggesting that exosome-mediated miR-21 transfer plays an important role in RIBE.…”

Section: Exosomesmentioning

confidence: 99%

Extracellular Vesicles and Vascular Injury: New Insights for Radiation Exposure

Flamant¹,

Tamarat²

2016

Radiation Research

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This article reviews our current knowledge about cell-derived extracellular vesicles (EVs), including microparticles and exosomes, and their emergence as mediators of a new important mechanism of cell-to-cell communication. Particular emphasis has been given to the increasing involvement of EVs in the field of radiation-induced vascular injury. Although EVs have been considered for a long time as cell “dust”, they in fact precisely reflect the physiological state of the cells. The role of microparticles and exosomes in mediating vascular dysfunction suggests that they may represent novel pathways in short- or long-distance paracrine intercellular signaling in vascular environment. In this article, the mechanisms involved in the biogenesis of microparticles and exosomes, their composition and participation in the pathogenesis of vascular dysfunction are discussed. Furthermore, this article highlights the concept of EVs as potent vectors of biological information and protagonists of an intercellular communication network. Special emphasis is made on EV-mediated microRNA transfer and on the principal consequences of such signal exchange on vascular injury and radiation-induced non-targeted effect. The recent progress in elucidating the biology of EVs has provided new insights for the field of radiation, advancing their use as diagnostic biomarkers or in therapeutic interventions.

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Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect

Cited by 146 publications

References 44 publications

Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect

Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect

Extracellular miR-1246 promotes lung cancer cell proliferation and enhances radioresistance by directly targeting DR5

Extracellular Vesicles and Vascular Injury: New Insights for Radiation Exposure

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