Ling Liu1, Meixiong Cheng1, Tian Zhang1, Yong Chen1, Yaqiu Wu2, Qi Wang3. 1. Department of Neurosurgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Section 2, 1st Ring Road, Chengdu, 610072, Sichuan Province, People's Republic of China. 2. Department of Neurosurgery Intensive Care Unit, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Section 2, 1st Ring Road, Chengdu, 610072, Sichuan Province, People's Republic of China. wuyaqiu@med.uestc.edu.cn. 3. Department of Neurosurgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Section 2, 1st Ring Road, Chengdu, 610072, Sichuan Province, People's Republic of China. wangqi@med.uestc.edu.cn.
Abstract
AIM: Our current study is conducted with intention to explore the regulatory mechanism of mesenchymal stem cell (MSC)-derived extracellular vesicle (EV)-miR-744-5p in glioma. METHODS: Expression patterns of TGFB1, TGFBR1, and miR-744-5p were determined. EVs were isolated from human MSCs, which were characterized. Then, macrophages were co-cultured with MSCs with ectopic miR-744-5p expression to explore its role in cell proliferation, invasion, and migration capabilities. A nude mouse model of glioma xenograft was developed to observe the tumorigenesis and metastasis ability of glioma in vivo. RESULTS: TGFB1 and TGFBR1 were upregulated in glioma. TGFB1 promoted M2 polarization of macrophages through theMAPK signaling, thereby promoting the progression of glioma. MSC-EVs suppressed TGFB1 expression in macrophages and inhibited M2 polarization of macrophages. MSC-EVs-miR-744-5p/TGFB1/MAPK axis inhibited M2 polarization of macrophages and reduced the malignant phenotypes of glioma cells. In vivo experiments verified that MSC-EVs-miR-744-5p inhibited the polarization of macrophage M2 and prevented glioma progression. CONCLUSION: Taken together, MSC-EVs-miR-744-5p may suppress the MAPK signaling activity by downregulating TGFB1, and then inhibit polarization of macrophages M2, thereby preventing the progression of glioma. Graphical Headlights 1. TGFB1 promotes the M2 polarization of macrophages via the MAPK signaling. 2. miR-744-5p carried by MSC-EVs targets and inhibits TGFB1. 3. MSC-EV-miR-744-5p inhibits M2 polarization of macrophages to prevent glioma progression. 4. miR-744-5p loaded by MSC-EVs may be a preventive strategy against glioma.
AIM: Our current study is conducted with intention to explore the regulatory mechanism of mesenchymal stem cell (MSC)-derived extracellular vesicle (EV)-miR-744-5p in glioma. METHODS: Expression patterns of TGFB1, TGFBR1, and miR-744-5p were determined. EVs were isolated from human MSCs, which were characterized. Then, macrophages were co-cultured with MSCs with ectopic miR-744-5p expression to explore its role in cell proliferation, invasion, and migration capabilities. A nude mouse model of glioma xenograft was developed to observe the tumorigenesis and metastasis ability of glioma in vivo. RESULTS: TGFB1 and TGFBR1 were upregulated in glioma. TGFB1 promoted M2 polarization of macrophages through theMAPK signaling, thereby promoting the progression of glioma. MSC-EVs suppressed TGFB1 expression in macrophages and inhibited M2 polarization of macrophages. MSC-EVs-miR-744-5p/TGFB1/MAPK axis inhibited M2 polarization of macrophages and reduced the malignant phenotypes of glioma cells. In vivo experiments verified that MSC-EVs-miR-744-5p inhibited the polarization of macrophage M2 and prevented glioma progression. CONCLUSION: Taken together, MSC-EVs-miR-744-5p may suppress the MAPK signaling activity by downregulating TGFB1, and then inhibit polarization of macrophages M2, thereby preventing the progression of glioma. Graphical Headlights 1. TGFB1 promotes the M2 polarization of macrophages via the MAPK signaling. 2. miR-744-5p carried by MSC-EVs targets and inhibits TGFB1. 3. MSC-EV-miR-744-5p inhibits M2 polarization of macrophages to prevent glioma progression. 4. miR-744-5p loaded by MSC-EVs may be a preventive strategy against glioma.
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Authors: Brigitta G Baumert; Monika E Hegi; Martin J van den Bent; Andreas von Deimling; Thierry Gorlia; Khê Hoang-Xuan; Alba A Brandes; Guy Kantor; Martin J B Taphoorn; Mohamed Ben Hassel; Christian Hartmann; Gail Ryan; David Capper; Johan M Kros; Sebastian Kurscheid; Wolfgang Wick; Roelien Enting; Michele Reni; Brian Thiessen; Frederic Dhermain; Jacoline E Bromberg; Loic Feuvret; Jaap C Reijneveld; Olivier Chinot; Johanna M M Gijtenbeek; John P Rossiter; Nicolas Dif; Carmen Balana; Jose Bravo-Marques; Paul M Clement; Christine Marosi; Tzahala Tzuk-Shina; Robert A Nordal; Jeremy Rees; Denis Lacombe; Warren P Mason; Roger Stupp Journal: Lancet Oncol Date: 2016-09-27 Impact factor: 54.433