Suppressing the secretion of exosomal miR-19b by gw4869 could regulate oxaliplatin sensitivity in colorectal cancer

Gu, Yuanyuan; Yu, Junchuan; Zhang, J F; Wang, C

doi:10.4149/neo_2018_180306n155

Cited by 28 publications

(22 citation statements)

References 32 publications

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“…Generally, exosome inhibitors cannot exert a significant effect on target cells (Figure 2B). At the same time, with reference to the reported materials, 10‐20 μ m GW4869 was usually adopted in similar experiments performed at different laboratories (Essandoh et al, 2015; Gu, Yu, Zhang, & Wang, 2019). Therefore, in the following experiments, 20 μ m was used as the operating concentration for GW4869.…”

Section: Resultsmentioning

confidence: 99%

Exosomal secretion may be a self‐protective mechanism of its source cells under environmental stress: A study on human bronchial epithelial cells treated with hydroquinone

Lian

et al. 2020

J of Applied Toxicology

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Accumulating evidence reveals that exosome plays an important role in cell-to-cell communication in both physiological and pathological processes by transferring bioactive molecules. However, the role of exosomal secretion in the adaption of its source cells to the stimuli of environmental chemicals remains elusive. In this study, we revealed that the exposure of hydroquinone (HQ; the main bioactive metabolite of benzene) to human bronchial epithelial cells (16HBE) resulted in decreased ability of cell proliferation and migration, and simultaneously DNA damage and micronuclei formation. Interestingly, when exosomal secretion of HQ treated 16HBE cells was inhibited with the inhibitor GW4869, cellular proliferation and migration were further significantly reduced; concurrently, their DNA damage and micronuclei formation were both further significantly aggravated. Herein, we conclude that exosomal secretion of 16HBE cells may be an important self-protective function against the toxic effects induced by HQ.

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Section: Resultsmentioning

confidence: 99%

Exosomal secretion may be a self‐protective mechanism of its source cells under environmental stress: A study on human bronchial epithelial cells treated with hydroquinone

Lian

et al. 2020

J of Applied Toxicology

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“…This is attributed to the apoptosis- and inflammation-related downstream targets of EV-associated and transferred miR-146a and miR-10a, including IRAK1 and TRAF6, and BIM respectively ( Xiao G. Y. et al, 2016 ). However, if these anti-apoptotic EVs are trafficked to off-target sites (i.e., tumors), they can significantly reduce the sensitivity of tumor cells to chemotherapy treatment, as demonstrated by EV-mediated transfer of miR-19b ( Gu Y. Y. et al, 2019 ). Therefore, stringent regulation of EV-associated bioactive cargo and components of interest is critical in developing EVs for therapeutic application.…”

Section: Evs As Nanocarriers Of Functional Cargomentioning

confidence: 99%

“…As such, a global view of EV-based therapeutic action is needed. The biological cargo harbored by EVs, including proteins ( Al-Nedawi et al, 2008 ; Yim et al, 2016 ; Yuan et al, 2017 ; Zhang G. et al, 2017 ; Roefs et al, 2020 ), nucleic acids ( Ratajczak et al, 2006 ; Liang et al, 2016 ; Xiao G. Y. et al, 2016 ; Song et al, 2017 ; Gu et al, 2018 ; Shi et al, 2018 ; Gu Y. Y. et al, 2019 ; Basalova et al, 2020 ), and lipids ( Lindemann, 1989 ; Fadok et al, 2000 ; Gurnani et al, 2004 ; Yuyama et al, 2014 ) [reviewed in Greening et al (2017) , Skotland et al (2019) , O’Brien et al (2020) ] ( Table 2 ), greatly influence their clinical potential. The protein and lipid expression of EVs yield insights into their surface receptor mediated interactions with, and effects on recipient cells, including their fusion and uptake ( Christianson et al, 2013 ; Purushothaman et al, 2016 ; Berenguer et al, 2018 ), while their genetic landscape sheds light on the EVs’ reprogramming potential through regulation of protein expression ( Ratajczak et al, 2006 ; Skog et al, 2008 ; Abels et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

Claridge

Lozano

Poh

et al. 2021

Front. Cell Dev. Biol.

111

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Extracellular vesicles (EVs) hold great promise as therapeutic modalities due to their endogenous characteristics, however, further bioengineering refinement is required to address clinical and commercial limitations. Clinical applications of EV-based therapeutics are being trialed in immunomodulation, tissue regeneration and recovery, and as delivery vectors for combination therapies. Native/biological EVs possess diverse endogenous properties that offer stability and facilitate crossing of biological barriers for delivery of molecular cargo to cells, acting as a form of intercellular communication to regulate function and phenotype. Moreover, EVs are important components of paracrine signaling in stem/progenitor cell-based therapies, are employed as standalone therapies, and can be used as a drug delivery system. Despite remarkable utility of native/biological EVs, they can be improved using bio/engineering approaches to further therapeutic potential. EVs can be engineered to harbor specific pharmaceutical content, enhance their stability, and modify surface epitopes for improved tropism and targeting to cells and tissues in vivo. Limitations currently challenging the full realization of their therapeutic utility include scalability and standardization of generation, molecular characterization for design and regulation, therapeutic potency assessment, and targeted delivery. The fields’ utilization of advanced technologies (imaging, quantitative analyses, multi-omics, labeling/live-cell reporters), and utility of biocompatible natural sources for producing EVs (plants, bacteria, milk) will play an important role in overcoming these limitations. Advancements in EV engineering methodologies and design will facilitate the development of EV-based therapeutics, revolutionizing the current pharmaceutical landscape.

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“…In order to confirm whether the promotive effect of M2 macrophage on aerobic glycolysis and DDP-resistance in cancer cells was achieved through producing exosomes, we first tried to isolate exosome from the conditioned medium of M2 macrophages. We successfully purified exosomes, as evidenced by the expression of exosomal markers TSG101 and CD63, which could be abolished by the treatment of a widley-used exosome inhibitor GW4869 (Essandoh et al, 2015;Chen et al, 2019;Gu et al, 2019) (Figure 2A). The purified exosomes derived from M2 macrophage displayed as small round vesicles with the average diameter of either 58 ± 10 nm or 100 nm depending on the method utilized for particle size analysis (Supplementary Figure 1).…”

Section: Exosomes Derived From M2 Macrophages Can Enhance Aerobic Glymentioning

confidence: 99%

Exosomes Derived From Macrophages Enhance Aerobic Glycolysis and Chemoresistance in Lung Cancer by Stabilizing c-Myc via the Inhibition of NEDD4L

Wang

Pan

et al. 2021

Front. Cell Dev. Biol.

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As one of the most common and lethal cancer, lung cancer severely threatens the health of human. It has been reported that tumor-associated macrophages promote initiation, progression, as well as chemoresistance in human cancers. However, the underneath molecular mechanism that drives chemoresistance in lung cancer is yet not fully characterized. In this article, we demonstrated that M2 macrophage-derived exosomes (MDE) is the key factor to promote cisplatin-resistance in lung cancer. MDE exhibited high expression level of several miRNA including miR-3679-5p. Mechanistically, miR-3679-5p was delivered to lung cancer cells by MDE, downregulating the expression of a known E3 ligase, NEDD4L, which has been identified as a key regulator controlling the stability of c-Myc. Such decreased NEDD4L expression level resulted in the stabilization of c-Myc and elevated glycolysis. The enhanced glycolysis drives the chemoresistance in lung cancer. Taken together, our findings not only show that M2 macrophage induce chemoresistance in lung cancer through MDE mediated miR-3679-5R/NEDD4L/c-Myc signaling cascade, but also shed the light on the mechanism of the cross-talk between M2 macrophage and lung cancers. By pinpointing a potential novel survival signaling pathway, our data could provide a new potential therapeutic target for lung cancer treatment and management.

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Suppressing the secretion of exosomal miR-19b by gw4869 could regulate oxaliplatin sensitivity in colorectal cancer

Cited by 28 publications

References 32 publications

Exosomal secretion may be a self‐protective mechanism of its source cells under environmental stress: A study on human bronchial epithelial cells treated with hydroquinone

Exosomal secretion may be a self‐protective mechanism of its source cells under environmental stress: A study on human bronchial epithelial cells treated with hydroquinone

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

Exosomes Derived From Macrophages Enhance Aerobic Glycolysis and Chemoresistance in Lung Cancer by Stabilizing c-Myc via the Inhibition of NEDD4L

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