Wenjia Ma1, Yu Zhou1, Min Liu1, Qilin Qin1, Yan Cui2. 1. Department of Neurosurgery, The Second Xiangya Hospital, Central South University, No. 139, Renmin Road, Changsha, 410011, Hunan, People's Republic of China. 2. Department of Neurosurgery, The Second Xiangya Hospital, Central South University, No. 139, Renmin Road, Changsha, 410011, Hunan, People's Republic of China. 148202093@csu.edu.cn.
Abstract
BACKGROUND: To explore the mechanism of LINC00470 in serum exosomes from glioma patients regulating the autophagy and proliferation of glioma cells. METHODS: Exosomes were extracted from glioma patients (GBM-exo). Expression of LINC00470 in exosomes was analyzed with the clinicopathological characteristics of glioma patients. Glioma mouse model was established. The effects of LINC00470, miR-580-3p and WEE1 on cell autophagy and proliferation, as well as the activation of PI3K/AKT/mTOR pathway were measured. Dual luciferase reporter assay and RNA immunoprecipitation (RIP) were conducted to validate the binding of LINC00470 and miR-580-3p and of miR-580-3p and WEE1. RESULTS: LINC00470 overexpressed in GBM-exo and associated with disease severity and postoperative survival time of glioma patients. GBM-exo deteriorated tumor progression in nude mice. Cells incubated with GBM-exo or transfected with pcDNA3.1-LINC00470/miR-580-3p inhibitor/pcDNA3.1-WEE1 had less autophagosome, downregulated LC3-II/LC3-I and Beclin1 expression levels and increased expression of p62 as well as strengthened proliferation ability. The PI3K/AKT/mTOR pathway was activated. LINC00470 competitively bound to miR-580-3p with WEE1. CONCLUSION: LINC00470 in GBM-exo can bind to miR-580-3p in glioma cells to regulate WEE1 expression and activate the PI3K/AKT/mTOR pathway, thereby inhibiting autophagy and enhancing the proliferation of glioma cells.
BACKGROUND: To explore the mechanism of LINC00470 in serum exosomes from gliomapatients regulating the autophagy and proliferation of glioma cells. METHODS: Exosomes were extracted from gliomapatients (GBM-exo). Expression of LINC00470 in exosomes was analyzed with the clinicopathological characteristics of gliomapatients. Gliomamouse model was established. The effects of LINC00470, miR-580-3p and WEE1 on cell autophagy and proliferation, as well as the activation of PI3K/AKT/mTOR pathway were measured. Dual luciferase reporter assay and RNA immunoprecipitation (RIP) were conducted to validate the binding of LINC00470 and miR-580-3p and of miR-580-3p and WEE1. RESULTS:LINC00470 overexpressed in GBM-exo and associated with disease severity and postoperative survival time of gliomapatients. GBM-exo deteriorated tumor progression in nude mice. Cells incubated with GBM-exo or transfected with pcDNA3.1-LINC00470/miR-580-3p inhibitor/pcDNA3.1-WEE1 had less autophagosome, downregulated LC3-II/LC3-I and Beclin1 expression levels and increased expression of p62 as well as strengthened proliferation ability. The PI3K/AKT/mTOR pathway was activated. LINC00470 competitively bound to miR-580-3p with WEE1. CONCLUSION:LINC00470 in GBM-exo can bind to miR-580-3p in glioma cells to regulate WEE1 expression and activate the PI3K/AKT/mTOR pathway, thereby inhibiting autophagy and enhancing the proliferation of glioma cells.