MicroRNA125b inhibitor sensitizes human primary g

Authors: Yi Wan Guan Sun Shuguang Zhang Zhimin Wang Lei Shi

Publish Date: 2013/07/09

Volume: 49, Issue: 8, Pages: 599-607

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Abstract

Malignant gliomas are treated with a combination of surgery radiation and temozolomide TMZ but these therapies ultimately fail due to tumor recurrence In this study we aimed to identify the combined effects of miR125b and TMZ involved in the invasive pathogenesis of glioblastoma cells The effects of miR125b and TMZ on cell invasion were analyzed by Transwell assays Unexpectedly either overexpression or downregulation of miR125b has no function on glioblastoma cell invasion However knockdown of miR125b could enhance the effects of TMZ on glioblastoma cell invasion Conversely overexpression of miR125b could decrease such effects of TMZ Further research on the mechanism demonstrated that such function of miR125b knockdown on enhancing the effects of TMZ was involved in downregulation of Notch1 Notch1 was overexpressed in glioblastoma cells and found by us that downregulation of Notch1 expression decreased the cell invasion of glioblastoma cells Knockdown of miR125b combined with TMZ enhancely downregulated Notch1 and inhibited cell invasion of malignant glioblastoma These findings indicate that the combination of miR125b inhibitor and TMZ treatment could effectively inhibit the glioblastoma cell invasion by inhibiting Notch1 expressionThis work was supported by the China Natural Science Foundation 81000963 and 81201976 Jiangsu Province’s 333 Talent Program BRA2011046 Jiangsu Province’s Natural Science Foundation BK2012670 the Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU the Priority Academic Program Development of Jiangsu Higher Education Institutions the Kunshan Social Development Foundation Grant Number KS1006 KS1009 and the Suzhou Social Development Foundation SYS201063

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