Font Size: a A A

The Role And Mechanism Of EGFR/AKT Pathway Mediated By MiR-183 Via Targeting LRIG1 In Glioblastoma Radioresistance

Posted on:2019-06-24Degree:MasterType:Thesis
Country:ChinaCandidate:H Y FanFull Text:PDF
GTID:2334330548959782Subject:Outside of the surgery
Abstract/Summary:PDF Full Text Request
Background and objectiveGlioma is the most common cause of cancer-related death.Therapy based on radiation seemed to effectively,while the radioresistance of several glioblastoma cells abolished the therapy.Thus,to employ the potential mechanism underlying the radioresistance is essential for glioma treatment.This study establish radioresistant cell line U251 R,to explore the expression correlation of miR-183 and LRIG1 in glioma tissues and cells.To further explore the regulation mechanism of miR-183 and EGFR/AKT pathway,and the relationship to glioblastoma radioresistance,in order to provide novel insight into the mechanism of radiotherapy in glioma.MethodsRadioresistant cells were constructed using the X-ray radiation.Cell viability and apoptosis were detect using CCK-8 and Annexin-V/propidium iodide(PI),respectively.Real-time PCR and western blot were performed to determine gene expression.Luciferase reporter assay was carried out to detect the relationship between miR-183 and LRIG1.Mice xenotransplant model of glioma was established to detect the role of miR-183 in vivo.ResultsThe expression of mi R-183 was increased,while LRIG1 was decreased in resistant tissues rather than in sensitive tissues.The expression of LRIG1 was lower in radioresistant gliblastoma cell line U251 R rather than in normal glioblastoma cell line U251.Overexpressed miR-183 suppressed cell apoptosis in radioresistance U251 R cells(U251R).MiR-183 targets LRIG1 to regulate its expression.U251 R cells transfected miR-183 inhibitor promoted the expression of LRIG1,and decreased the expression of EFGR and p-Akt,while U251 R cells cotransfected with shRNA-LRIG1 abolished the effects of miR-183 knockdown.U251 cells transfected with miR-183 mimic decreased the expression of LRIG1,and promoted the expression of EFGR and p-Akt,while cells cotransfected with pcDNA-LRIG1 abolished the effects of miR-183 overexpression.In vivo experiments demonstratedthat miR-183 inhibitor suppressed tumor growth,while miR-183 mimic promoted tumor growth.ConclusionCell radiaoresistance affected the effects of radiotherapy in glioma,miR-183 governs the radioresistance via targeting LRIG1,while EFGR/Akt mediated the mechanism of the radioresistance.
Keywords/Search Tags:Glioma, miR-183, Radioresistance, LRIG1, EGFR/Akt
PDF Full Text Request
Related items