4Department of Neurosurgery, Qilu Hospital of Shandong University Dezhou Hospital, 253000, Dezhou, Shandong, China5Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu and Weiqi Street, 250021, Jinan, Shandong, China2Shandong Key Laboratory of Brain Function Remodeling, Qilu Hospital, 250012, Jinan, Shandong, China3The Second Hospital, Cheeloo College of Medicine, Shandong University, 250033, Jinan, Shandong, China1Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, 107 Wenhua Xi Road, 250012, Jinan, Shandong, China
Background: The microenvironment of hypoxia is an important factor contributing to the development of glioblastoma . MicroRNA-588 and its potential target Roundabout-directed receptor 1 have been reported to promote tumor invasion and proliferation in diseases such as gastric, pancreatic and hepatocellular carcinoma, while their function in GBM and response to hypoxic states remain elusive. Methods: A microarray was leveraged to identify differentially expressed microRNAs in U251 glioma cells c...更多
Background: The microenvironment of hypoxia is an important factor contributing to the development of glioblastoma . MicroRNA-588 and its potential target Roundabout-directed receptor 1 have been reported to promote tumor invasion and proliferation in diseases such as gastric, pancreatic and hepatocellular carcinoma, while their function in GBM and response to hypoxic states remain elusive. Methods: A microarray was leveraged to identify differentially expressed microRNAs in U251 glioma cells cultured under normoxic and hypoxic conditions. The expression of miR-588 was assessed using quantitative real-time PCR . Gain- and loss-of-function studies were used to evaluate the role of miR-588 under hypoxic and normoxic conditions. Cell invasion, migration, proliferation, and vasculogenic mimicry formation experiments were performed. The relationship between miR-588 and ROBO1 was confirmed using western blot and luciferase reporter assays. Intracranial xenograft tumor mouse models were used to study the function of miR-588 in vivo. Results: The expression of miR-588 was significantly upregulated in hypoxic glioma cells relative to normoxic glioma cells. miR-588 inhibited the invasive, migratory and VM-forming abilities of glioma cells in vitro and in vivo. Mechanistically, roundabout guidance receptor 1 is a direct, functionally relevant target of miR-588 in glioma. ROBO1 knockdown suppressed the expression of matrix metallopeptidase 2 and matrix metallopeptidase 9 , thereby inhibiting the invasive, migratory and VM-forming abilities of glioma. Conclusions: MiR-588 regulated the behaviors of hypoxic glioma cells by targeting ROBO1. miR-588 can be used as a prognostic marker for glioma and has potential implications in glioma gene therapy.收起
