C6-ceramide treatment inhibits the proangiogenic activity of multiple myeloma exosomes via the miR-29b/Akt pathway
العنوان: | C6-ceramide treatment inhibits the proangiogenic activity of multiple myeloma exosomes via the miR-29b/Akt pathway |
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المؤلفون: | Yanfang Chen, Jing Liu, Langni Liu, Liping Liu, Ji C. Bihl, Qinmao Ye, Qian Cheng |
المصدر: | Journal of Translational Medicine Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-9 (2020) |
بيانات النشر: | Springer Science and Business Media LLC, 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | 0301 basic medicine, Ceramide, Angiogenesis, lcsh:Medicine, Ceramides, Exosomes, MiR-29b, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple myeloma, Humans, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, Tube formation, Research, lcsh:R, General Medicine, C6-ceramide, Microvesicles, carbohydrates (lipids), Endothelial stem cell, MicroRNAs, Vascular endothelial growth factor A, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Cancer research, lipids (amino acids, peptides, and proteins), Proto-Oncogene Proteins c-akt, Akt pathway |
الوصف: | Background The increased bone marrow angiogenesis is involved in the progression of multiple myeloma (MM) with the underlying mechanism poorly understood. Cancer-released exosomes could play an important role in the pathological angiogenesis through exosomal microRNAs (miRs) delivery. It is reported that miR-29b played an important role in regulating the tumor angiogenesis. Methods In this study, we explored the role of C6-ceramide (C6-cer, a Ceramide pathway activator) in the angiogenic effect of MM exosomes and its potential mechanism. MM cells (OPM2 and RPMI-8226) treated with C6-cer were studied for its effects on the endothelial cell (EC) functions. Results Our results showed that exosomes released from MM cells treated by C6-cer (ExoC6-cer) significantly inhibited the proliferation, migration and tube formation of ECs. For mechanism studies, we found that the level of miR-29b was increased in ECs treated by ExoC6-cer, while mRNA and protein expressions of Akt3, PI3K and VEGFA were decreased in ECs, indicating the involvement of Akt pathway. Furthermore, downregulation of miR-29b by inhibitor administration could prevent the ExoC6-cer-induced cell proliferation, migration and angiogenesis of ECs, accompanied with the increased expressions of Akt3, PI3K and VEGFA. Conclusions Collectively, our data suggest that ExoC6-cer-mediated miR-29b expression participates in the progression of MM through suppressing the proliferation, migration and angiogenesis of ECs by targeting Akt signal pathway. |
تدمد: | 1479-5876 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::949a953014dd837e3588b8914c373b8f https://doi.org/10.1186/s12967-020-02468-9 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....949a953014dd837e3588b8914c373b8f |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14795876 |
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