The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Mohammad Javan - One of the best experts on this subject based on the ideXlab platform.
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microRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells
Cellular Oncology, 2017Co-Authors: Katayoon Pakravan, Sadegh Babashah, Majid Sadeghizadeh, Seyed Javad Mowla, Majid Mossahebi-mohammadi, Farangis Ataei, Nasim Dana, Mohammad JavanAbstract:Background Human mesenchymal stem cells (MSCs) have been shown to be involved in the formation and modulation of tumor stroma and in interacting with tumor cells, partly through their secretome. Exosomes are nano-sized intraluminal multi-vesicular bodies secreted by most types of cells and have been found to mediate intercellular communication through the transfer of genetic information via coding and non-coding RNAs to recipient cells. Since exosomes are considered as protective and enriched sources of shuttle microRNAs (miRNAs), we hypothesized that exosomal transfer of miRNAs from MSCs may affect tumor cell behavior, particularly angiogenesis. Methods Exosomes derived from MSCs were isolated and characterized by scanning electron microscopy analyses, dynamic light scattering measurements, and Western blotting. Fold changes in miR-100 expression levels were calculated in exosomes and their corresponding donor cells by qRT-PCR. The effects of exosomal transfer of miR-100 from MSCs were assessed by qRT-PCR and Western blotting of the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. The quantification of secreted VEGF protein was determined by enzyme-linked immunosorbent assay. The putative paracrine effects of MSC-derived exosomes on tumor angiogenesis were explored by in vitro angiogenesis assays including endothelial cell proliferation, migration and tube formation assays. Results We found that MSC-derived exosomes induce a significant and dose-dependent decrease in the expression and secretion of vascular endothelial growth factor (VEGF) through modulating the mTOR/HIF-1α signaling axis in breast cancer-derived cells. We also found that miR-100 is enriched in MSC-derived exosomes and that its transfer to breast cancer-derived cells is associated with the down-regulation of VEGF in a time-dependent manner. The putative role of exosomal miR-100 transfer in regulating VEGF expression was substantiated by the ability of anti-miR-100 to rescue the inhibitory effects of MSC-derived exosomes on the expression of VEGF in breast cancer-derived cells. In addition, we found that down-regulation of VEGF mediated by MSC-derived exosomes can affect the vascular behavior of endothelial cells in vitro. Conclusions Overall, our findings suggest that exosomal transfer of miR-100 may be a novel mechanism underlying the paracrine effects of MSC-derived exosomes and may provide a means by which these vesicles can modulate vascular responses within the microenvironment of breast cancer cells.
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microRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells.
Cellular oncology (Dordrecht), 2017Co-Authors: Katayoon Pakravan, Sadegh Babashah, Majid Sadeghizadeh, Seyed Javad Mowla, Majid Mossahebi-mohammadi, Farangis Ataei, Nasim Dana, Mohammad JavanAbstract:Human mesenchymal stem cells (MSCs) have been shown to be involved in the formation and modulation of tumor stroma and in interacting with tumor cells, partly through their secretome. Exosomes are nano-sized intraluminal multi-vesicular bodies secreted by most types of cells and have been found to mediate intercellular communication through the transfer of genetic information via coding and non-coding RNAs to recipient cells. Since exosomes are considered as protective and enriched sources of shuttle microRNAs (miRNAs), we hypothesized that exosomal transfer of miRNAs from MSCs may affect tumor cell behavior, particularly angiogenesis. Exosomes derived from MSCs were isolated and characterized by scanning electron microscopy analyses, dynamic light scattering measurements, and Western blotting. Fold changes in miR-100 expression levels were calculated in exosomes and their corresponding donor cells by qRT-PCR. The effects of exosomal transfer of miR-100 from MSCs were assessed by qRT-PCR and Western blotting of the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. The quantification of secreted VEGF protein was determined by enzyme-linked immunosorbent assay. The putative paracrine effects of MSC-derived exosomes on tumor angiogenesis were explored by in vitro angiogenesis assays including endothelial cell proliferation, migration and tube formation assays. We found that MSC-derived exosomes induce a significant and dose-dependent decrease in the expression and secretion of vascular endothelial growth factor (VEGF) through modulating the mTOR/HIF-1α signaling axis in breast cancer-derived cells. We also found that miR-100 is enriched in MSC-derived exosomes and that its transfer to breast cancer-derived cells is associated with the down-regulation of VEGF in a time-dependent manner. The putative role of exosomal miR-100 transfer in regulating VEGF expression was substantiated by the ability of anti-miR-100 to rescue the inhibitory effects of MSC-derived exosomes on the expression of VEGF in breast cancer-derived cells. In addition, we found that down-regulation of VEGF mediated by MSC-derived exosomes can affect the vascular behavior of endothelial cells in vitro. Overall, our findings suggest that exosomal transfer of miR-100 may be a novel mechanism underlying the paracrine effects of MSC-derived exosomes and may provide a means by which these vesicles can modulate vascular responses within the microenvironment of breast cancer cells.
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microRNA 100 shuttled by mesenchymal stem cell derived exosomes suppresses in vitro angiogenesis through modulating the mtor hif 1α vegf signaling axis in breast cancer cells
Cellular Oncology, 2017Co-Authors: Katayoon Pakravan, Sadegh Babashah, Majid Sadeghizadeh, Seyed Javad Mowla, Farangis Ataei, Nasim Dana, Mohammad Javan, Majid MossahebimohammadiAbstract:Human mesenchymal stem cells (MSCs) have been shown to be involved in the formation and modulation of tumor stroma and in interacting with tumor cells, partly through their secretome. Exosomes are nano-sized intraluminal multi-vesicular bodies secreted by most types of cells and have been found to mediate intercellular communication through the transfer of genetic information via coding and non-coding RNAs to recipient cells. Since exosomes are considered as protective and enriched sources of shuttle microRNAs (miRNAs), we hypothesized that exosomal transfer of miRNAs from MSCs may affect tumor cell behavior, particularly angiogenesis. Exosomes derived from MSCs were isolated and characterized by scanning electron microscopy analyses, dynamic light scattering measurements, and Western blotting. Fold changes in miR-100 expression levels were calculated in exosomes and their corresponding donor cells by qRT-PCR. The effects of exosomal transfer of miR-100 from MSCs were assessed by qRT-PCR and Western blotting of the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. The quantification of secreted VEGF protein was determined by enzyme-linked immunosorbent assay. The putative paracrine effects of MSC-derived exosomes on tumor angiogenesis were explored by in vitro angiogenesis assays including endothelial cell proliferation, migration and tube formation assays. We found that MSC-derived exosomes induce a significant and dose-dependent decrease in the expression and secretion of vascular endothelial growth factor (VEGF) through modulating the mTOR/HIF-1α signaling axis in breast cancer-derived cells. We also found that miR-100 is enriched in MSC-derived exosomes and that its transfer to breast cancer-derived cells is associated with the down-regulation of VEGF in a time-dependent manner. The putative role of exosomal miR-100 transfer in regulating VEGF expression was substantiated by the ability of anti-miR-100 to rescue the inhibitory effects of MSC-derived exosomes on the expression of VEGF in breast cancer-derived cells. In addition, we found that down-regulation of VEGF mediated by MSC-derived exosomes can affect the vascular behavior of endothelial cells in vitro. Overall, our findings suggest that exosomal transfer of miR-100 may be a novel mechanism underlying the paracrine effects of MSC-derived exosomes and may provide a means by which these vesicles can modulate vascular responses within the microenvironment of breast cancer cells.
John S. Kuo - One of the best experts on this subject based on the ideXlab platform.
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microRNA 100 targets smrt ncor2 reduces proliferation and improves survival in glioblastoma animal models
PLOS ONE, 2013Co-Authors: Bahauddeen M. Alrfaei, Raghu Vemuganti, John S. KuoAbstract:Glioblastoma (GBM) is the most frequently diagnosed malignant human glioma, and current median patient survival is less than two years despite maximal surgery followed by temozolomide chemoradiation therapies. Novel microRNA-related therapies are now being developed for cancers such as GBM. Differential microRNA expression profiling revealed that miR-100 expression is down-regulated in GBM compared to normal controls. We report that miR-100 expression reduces GBM tumorigenicity. In vitro, four GBM lines (U87, U251, 22T, and 33T) demonstrated reduced proliferation 24 hours after transient miR100 overexpression via transfection. miR-100 triggered cell death an average 70% more than scrambled miR controls 24 hours after transient transfection (p < 0.01). miR-100 targeted inhibition of the “silencing mediator of retinoid or thyroid hormone receptor-2” (SMRT/NCOR2) gene was confirmed via reporter assays. Ki67 proliferation index was decreased 40% in tumor xenografts generated from stable miR-100 transfected GBM lines versus controls (p < 0.01). Furthermore, treatment of tumor xenografts with a single pre-mir-100 injection (60 pmol) significantly extended survival of mice bearing intracranial GBM xenografts 25% more than scrambled controls (p < 0.01; n=8). These studies establish miR-100’s effect on tumor GBM growth, and suggest clinical potential for microRNA-related GBM therapy.
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microRNA-100 Targets SMRT/NCOR2, Reduces Proliferation, and Improves Survival in Glioblastoma Animal Models
PloS one, 2013Co-Authors: Bahauddeen M. Alrfaei, Raghu Vemuganti, John S. KuoAbstract:Glioblastoma (GBM) is the most frequently diagnosed malignant human glioma, and current median patient survival is less than two years despite maximal surgery followed by temozolomide chemoradiation therapies. Novel microRNA-related therapies are now being developed for cancers such as GBM. Differential microRNA expression profiling revealed that miR-100 expression is down-regulated in GBM compared to normal controls. We report that miR-100 expression reduces GBM tumorigenicity. In vitro, four GBM lines (U87, U251, 22T, and 33T) demonstrated reduced proliferation 24 hours after transient miR100 overexpression via transfection. miR-100 triggered cell death an average 70% more than scrambled miR controls 24 hours after transient transfection (p < 0.01). miR-100 targeted inhibition of the “silencing mediator of retinoid or thyroid hormone receptor-2” (SMRT/NCOR2) gene was confirmed via reporter assays. Ki67 proliferation index was decreased 40% in tumor xenografts generated from stable miR-100 transfected GBM lines versus controls (p < 0.01). Furthermore, treatment of tumor xenografts with a single pre-mir-100 injection (60 pmol) significantly extended survival of mice bearing intracranial GBM xenografts 25% more than scrambled controls (p < 0.01; n=8). These studies establish miR-100’s effect on tumor GBM growth, and suggest clinical potential for microRNA-related GBM therapy.
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Abstract LB-245: microRNA-100 targets silencing mediator for retinoid receptors (SMRT), reduces proliferation, and improves survival in glioblastoma.
Molecular and Cellular Biology, 2013Co-Authors: Bahauddeen M. Alrfaei, Raghu Vemuganti, John S. KuoAbstract:Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Improved therapeutic approaches are needed for the most common primary adult brain cancer, Glioblastoma (GBM) because of the current dismal median survival of less than two years. We identified and tested the differentially expressed microRNA-100 (MiR-100) as a candidate ‘tumor suppressor’ in GBM. Quantitative PCR validated differential microRNA array results showing high miR-100 expression in normal cells and low expression in multiple GBM lines. MiR-100 overexpression via transfection of 4 GBM lines with miR-100 precursor (U87, U251, patient-derived 22T and 33T) reduced proliferation on MTS assays (average 50% ± 15; p < 0.05). TUNEL assays showed that transient transfection of 15 pmole of miR-100 per 500K GBM tumor cells triggered apoptosis 70% more than scrambled control miR after 24 hrs (p < 0.01). SMRT was identified as a candidate miR100 target in multiple miRNA databases, and validated with miR100-specific inhibition in a luciferase-SMRT 3′UTR reporter assay. In addition, a single dose of pre-mir-100 (60 pmol) injected directly into intracranial GBM xenografts significantly extended survival 30% more than mice injected with control scrambled miRNA (p < 0.01; n=8). GBM lines that stably overexpressed miR-100 two-fold over similar control transfected GBM lines were created for in vivo studies: 10x6 cells were implanted for tumor xenograft histology and survival analysis. Significantly reduced Ki-67 proliferation index was observed compared to control (mir-100 vector: 18±14% Ki-67+; empty vector: 100±11% Ki-67+; p < 0.01). Two-fold over-expression of miR-100 in vivo showed an average of 70% reduction in Ki-67 proliferation index. Furthermore, miR-100 overexpressing cells were associated with significantly smaller xenografts than injection of sibling control GBM cells. These studies establish the ‘tumor suppressor’ activity of miR-100 in GBM, which may lead to further developments as novel GBM therapies. Citation Format: Bahauddeen M. Alrfaei, Raghu Vemuganti, John S. Kuo. microRNA-100 targets silencing mediator for retinoid receptors (SMRT), reduces proliferation, and improves survival in glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-245. doi:10.1158/1538-7445.AM2013-LB-245
Sebastian Grundmann - One of the best experts on this subject based on the ideXlab platform.
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GW29-e1524 microRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy
Journal of the American College of Cardiology, 2018Co-Authors: Sebastian GrundmannAbstract:The interaction of circulating cells within the vascular wall is a critical event in chronic inflammatory processes, such as atherosclerosis, but the control of the vascular inflammatory state is still largely unclear. This study was undertaken to characterize the function of the endothelial-
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microRNA-100 Regulates Neovascularization by Suppression of Mammalian Target of Rapamycin in Endothelial and Vascular Smooth Muscle Cells
Circulation, 2011Co-Authors: Sebastian Grundmann, Imo E. Hoefer, Gerard Pasterkamp, Felix P. Hans, Sheena Kinniry, Jennifer Heinke, Thomas Helbing, Franziska Bluhm, Joost P.g. Sluijter, Christoph BodeAbstract:Background—The adaptive growth of blood vessels is an important protective mechanism in cardiovascular disease. However, the underlying regulatory mechanisms of this process are only partly understood. Recently, small endogenous RNAs (microRNAs [miRNAs]) were found to play an important role in embryonic and postnatal vascular development. Here, we used miRNA transcriptome analysis after induction of hind-limb ischemia in mice to screen for miRNAs involved in adaptive blood vessel growth following arterial occlusion. Methods and Results—Using miRNA arrays, we explored the miRNA expression profile during adaptive neovascularization. We describe specific changes in miRNA expression patterns and show that miRNA-100 is significantly downregulated after induction of hind-limb ischemia in mice. Our data demonstrate that miR-100 modulates proliferation, tube formation, and sprouting activity of endothelial cells and migration of vascular smooth muscle cells and functions as an endogenous repressor of the serine/t...
Christian Smolka - One of the best experts on this subject based on the ideXlab platform.
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microRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy
Circulation research, 2017Co-Authors: Franziska Pankratz, Catherine Hohnloser, Xavier Bemtgen, Caterina Jaenich, Sheena Kreuzaler, Imo E. Hoefer, Gerard Pasterkamp, Justin Mastroianni, Robert Zeiser, Christian SmolkaAbstract:Rationale: The interaction of circulating cells within the vascular wall is a critical event in chronic inflammatory processes such as atherosclerosis, but the control of the vascular inflammatory state is still largely unclear. Objective: This study was undertaken to characterize the function of the endothelial-enriched microRNA miR-100 during vascular inflammation and atherogenesis. Methods and Results: Based on a transcriptome analysis of endothelial cells after miR-100 overexpression, we identified miR-100 as potent suppressor of endothelial adhesion molecule expression, resulting in attenuated leukocyte-endothelial interaction in vitro and in vivo as shown by flow cytometry and intravital imaging approach. Mechanistically, miR-100 directly repressed several components of mTORC1-signalling, including mTOR and raptor, which resulted in a stimulation of endothelial autophagy and attenuated NF-κB signaling in vitro and in vivo. In a LDLR-deficient atherosclerotic mouse model, pharmacologic inhibition of miR-100 resulted in enhanced plaque lesion formation and a higher macrophage content of the plaque, whereas a systemic miR-100 replacement therapy had protective effects and attenuated atherogenesis, resulting in a decrease of plaque area by 45%. Finally, analysis of miR-100 expression in more than 70 samples obtained during carotid endarterectomy revealed that local miR-100 expression was inversely correlated with inflammatory cell content in patients. Conclusions: In summary, we describe an anti-inflammatory function of miR-100 in the vascular response to injury and inflammation and identify an important novel modulator of mTOR signaling and autophagy in the vascular system. Our findings of miR-100 as a potential protective "anti-athero-miR" suggest that the therapeutic replacement of this miRNA could be a potential strategy for the treatment of chronic inflammatory diseases such as atherosclerosis in the future.
Bahauddeen M. Alrfaei - One of the best experts on this subject based on the ideXlab platform.
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microRNA 100 targets smrt ncor2 reduces proliferation and improves survival in glioblastoma animal models
PLOS ONE, 2013Co-Authors: Bahauddeen M. Alrfaei, Raghu Vemuganti, John S. KuoAbstract:Glioblastoma (GBM) is the most frequently diagnosed malignant human glioma, and current median patient survival is less than two years despite maximal surgery followed by temozolomide chemoradiation therapies. Novel microRNA-related therapies are now being developed for cancers such as GBM. Differential microRNA expression profiling revealed that miR-100 expression is down-regulated in GBM compared to normal controls. We report that miR-100 expression reduces GBM tumorigenicity. In vitro, four GBM lines (U87, U251, 22T, and 33T) demonstrated reduced proliferation 24 hours after transient miR100 overexpression via transfection. miR-100 triggered cell death an average 70% more than scrambled miR controls 24 hours after transient transfection (p < 0.01). miR-100 targeted inhibition of the “silencing mediator of retinoid or thyroid hormone receptor-2” (SMRT/NCOR2) gene was confirmed via reporter assays. Ki67 proliferation index was decreased 40% in tumor xenografts generated from stable miR-100 transfected GBM lines versus controls (p < 0.01). Furthermore, treatment of tumor xenografts with a single pre-mir-100 injection (60 pmol) significantly extended survival of mice bearing intracranial GBM xenografts 25% more than scrambled controls (p < 0.01; n=8). These studies establish miR-100’s effect on tumor GBM growth, and suggest clinical potential for microRNA-related GBM therapy.
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microRNA-100 Targets SMRT/NCOR2, Reduces Proliferation, and Improves Survival in Glioblastoma Animal Models
PloS one, 2013Co-Authors: Bahauddeen M. Alrfaei, Raghu Vemuganti, John S. KuoAbstract:Glioblastoma (GBM) is the most frequently diagnosed malignant human glioma, and current median patient survival is less than two years despite maximal surgery followed by temozolomide chemoradiation therapies. Novel microRNA-related therapies are now being developed for cancers such as GBM. Differential microRNA expression profiling revealed that miR-100 expression is down-regulated in GBM compared to normal controls. We report that miR-100 expression reduces GBM tumorigenicity. In vitro, four GBM lines (U87, U251, 22T, and 33T) demonstrated reduced proliferation 24 hours after transient miR100 overexpression via transfection. miR-100 triggered cell death an average 70% more than scrambled miR controls 24 hours after transient transfection (p < 0.01). miR-100 targeted inhibition of the “silencing mediator of retinoid or thyroid hormone receptor-2” (SMRT/NCOR2) gene was confirmed via reporter assays. Ki67 proliferation index was decreased 40% in tumor xenografts generated from stable miR-100 transfected GBM lines versus controls (p < 0.01). Furthermore, treatment of tumor xenografts with a single pre-mir-100 injection (60 pmol) significantly extended survival of mice bearing intracranial GBM xenografts 25% more than scrambled controls (p < 0.01; n=8). These studies establish miR-100’s effect on tumor GBM growth, and suggest clinical potential for microRNA-related GBM therapy.
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Abstract LB-245: microRNA-100 targets silencing mediator for retinoid receptors (SMRT), reduces proliferation, and improves survival in glioblastoma.
Molecular and Cellular Biology, 2013Co-Authors: Bahauddeen M. Alrfaei, Raghu Vemuganti, John S. KuoAbstract:Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Improved therapeutic approaches are needed for the most common primary adult brain cancer, Glioblastoma (GBM) because of the current dismal median survival of less than two years. We identified and tested the differentially expressed microRNA-100 (MiR-100) as a candidate ‘tumor suppressor’ in GBM. Quantitative PCR validated differential microRNA array results showing high miR-100 expression in normal cells and low expression in multiple GBM lines. MiR-100 overexpression via transfection of 4 GBM lines with miR-100 precursor (U87, U251, patient-derived 22T and 33T) reduced proliferation on MTS assays (average 50% ± 15; p < 0.05). TUNEL assays showed that transient transfection of 15 pmole of miR-100 per 500K GBM tumor cells triggered apoptosis 70% more than scrambled control miR after 24 hrs (p < 0.01). SMRT was identified as a candidate miR100 target in multiple miRNA databases, and validated with miR100-specific inhibition in a luciferase-SMRT 3′UTR reporter assay. In addition, a single dose of pre-mir-100 (60 pmol) injected directly into intracranial GBM xenografts significantly extended survival 30% more than mice injected with control scrambled miRNA (p < 0.01; n=8). GBM lines that stably overexpressed miR-100 two-fold over similar control transfected GBM lines were created for in vivo studies: 10x6 cells were implanted for tumor xenograft histology and survival analysis. Significantly reduced Ki-67 proliferation index was observed compared to control (mir-100 vector: 18±14% Ki-67+; empty vector: 100±11% Ki-67+; p < 0.01). Two-fold over-expression of miR-100 in vivo showed an average of 70% reduction in Ki-67 proliferation index. Furthermore, miR-100 overexpressing cells were associated with significantly smaller xenografts than injection of sibling control GBM cells. These studies establish the ‘tumor suppressor’ activity of miR-100 in GBM, which may lead to further developments as novel GBM therapies. Citation Format: Bahauddeen M. Alrfaei, Raghu Vemuganti, John S. Kuo. microRNA-100 targets silencing mediator for retinoid receptors (SMRT), reduces proliferation, and improves survival in glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-245. doi:10.1158/1538-7445.AM2013-LB-245