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The invasive behavior of glioblastoma multiforme (GBM) cells is one of themost important reasons for the poor prognosis of this cancer. For invasion, tumorcells must acquire an ability to digest the extracellular matrix and infiltratethe normal tissue bordering the tumor. Preventing this by altering effector moleculescan significantly improve a patient's prognosis. Accumulating evidence suggeststhat miRNAs are involved in multiple biological functions, including cell invasion,by altering the expression of multiple target genes. The expression levels ofmiR-218 correlate with the invasive potential of GBM cells. In this study, wefound that miR-218 expression was low in glioma tissues, especially in GBM. Thedata showed an inverse correlation in 60 GBM tissues between the levels of miR-218and MMP mRNAs (MMP-2, -7 and -9). Additionally, ectopic expression of miR-218suppressed the invasion of GBM cells whereas inhibition of miR-218 expressionenhanced the invasive ability. Numerous members of the MMP family are downstreameffectors of the Wnt/LEF1 pathway. Target prediction databases and luciferasedata showed that LEF1 is a new direct target of miR-218. Importantly, westernblot assays demonstrated that miR-218 can reduce protein levels of LEF1 and MMP-9.We, therefore, hypothesize that miR-218 directly targets LEF1, resulting in reducedsynthesis of MMP-9. Results suggest that miR-218 is involved in the invasive behaviorof GBM cells and by targeting LEF1 and blocking the invasive axis, miR-218-LEF1-MMPs,it may be useful for developing potential clinical strategies.

MiR-218 reverses high invasiveness of glioblastoma cells by targeting the oncogenic transcription factor LEF1