Jie Yao1,2, Zefen Wang3, Yong Cheng4, Chao Ma5, Yahua Zhong6, Yilei Xiao7, Xu Gao8, Zhiqiang Li9. 1. Human Genetic Resources Conservation Center of Hubei Province, Wuhan, 430071, China. 2. Tumor Precision Diagnosis and Treatment Technology and Translation Medicine, Hubei Engineering Research Center, Wuhan, 430071, China. 3. Department of Physiology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China. 4. Department of Neurology, Hankou Hospital, General Hospital of Central Theater Command of Chinese People's Liberation Army, Wuhan, 430014, China. 5. Department of Neurosurgery, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuhan, 430071, Hubei, China. 6. Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. 7. Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, 252000, China. 8. Department of Neurosurgery, General Hospital of Northern Theater Command of People's Liberation Army, Shenyang, 110000, China. 9. Department of Neurosurgery, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuhan, 430071, Hubei, China. lizhiqiang@whu.edu.cn.
Abstract
BACKGROUND: Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells. METHODS: First, we identified seven differentially expressed miRNAs in infiltrating macrophages and detected the expression of these seven miRNAs in M2 macrophages. We then selected hsa-miR-15a-5p (miR-15a) and hsa-miR-92a-3p (miR-92a) for follow-up studies, and confirmed that miR-15a and miR-92a were under-expressed in M2 macrophage exosomes. Subsequently, we demonstrated that M2 macrophage-derived exosomes promoted migration and invasion of glioma cells, while exosomal miR-15a and miR-92a had the opposite effects on glioma cells. Next, we performed the target gene prediction in four databases and conducted target gene validation by qRT-PCR, western blot and dual luciferase reporter gene assays. RESULTS: The results revealed that miR-15a and miR-92a were bound to CCND1 and RAP1B, respectively. Western blot assays demonstrated that interference with the expression of CCND1 or RAP1B reduced the phosphorylation level of AKT and mTOR, indicating that both CCND1 and RAP1B can activate the PI3K/AKT/mTOR signaling pathway. CONCLUSION: Collectively, these findings indicate that M2 macrophage-derived exosomal miR-15a and miR-92a inhibit cell migration and invasion of glioma cells through PI3K/AKT/mTOR signaling pathway.
BACKGROUND:Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells. METHODS: First, we identified seven differentially expressed miRNAs in infiltrating macrophages and detected the expression of these seven miRNAs in M2 macrophages. We then selected hsa-miR-15a-5p (miR-15a) and hsa-miR-92a-3p (miR-92a) for follow-up studies, and confirmed that miR-15a and miR-92a were under-expressed in M2 macrophage exosomes. Subsequently, we demonstrated that M2 macrophage-derived exosomes promoted migration and invasion of glioma cells, while exosomal miR-15a and miR-92a had the opposite effects on glioma cells. Next, we performed the target gene prediction in four databases and conducted target gene validation by qRT-PCR, western blot and dual luciferase reporter gene assays. RESULTS: The results revealed that miR-15a and miR-92a were bound to CCND1 and RAP1B, respectively. Western blot assays demonstrated that interference with the expression of CCND1 or RAP1B reduced the phosphorylation level of AKT and mTOR, indicating that both CCND1 and RAP1B can activate the PI3K/AKT/mTOR signaling pathway. CONCLUSION: Collectively, these findings indicate that M2 macrophage-derived exosomal miR-15a and miR-92a inhibit cell migration and invasion of glioma cells through PI3K/AKT/mTOR signaling pathway.
Authors: Changbin Zhu; Dana Mustafa; Ping-Pin Zheng; Marcel van der Weiden; Andrea Sacchetti; Maarten Brandt; Ihsan Chrifi; Dennie Tempel; Pieter J M Leenen; Dirk Jan Duncker; Caroline Cheng; Johan M Kros Journal: Neuro Oncol Date: 2017-05-01 Impact factor: 12.300
Authors: Ladan Mashouri; Hassan Yousefi; Amir Reza Aref; Ali Mohammad Ahadi; Fatemeh Molaei; Suresh K Alahari Journal: Mol Cancer Date: 2019-04-02 Impact factor: 27.401