title: MiR-218 reverses high invasiveness of glioblastoma cells by targeting             the oncogenic transcription factor LEF1.
abstract: The invasive behavior of glioblastoma multiforme (GBM) cells is one of the             most important reasons for the poor prognosis of this cancer. For invasion, tumor             cells must acquire an ability to digest the extracellular matrix and infiltrate             the normal tissue bordering the tumor. Preventing this by altering effector molecules             can significantly improve a patient's prognosis. Accumulating evidence suggests             that miRNAs are involved in multiple biological functions, including cell invasion,             by altering the expression of multiple target genes. The expression levels of             miR-218 correlate with the invasive potential of GBM cells. In this study, we             found that miR-218 expression was low in glioma tissues, especially in GBM. The             data showed an inverse correlation in 60 GBM tissues between the levels of miR-218             and MMP mRNAs (MMP-2, -7 and -9). Additionally, ectopic expression of miR-218             suppressed the invasion of GBM cells whereas inhibition of miR-218 expression             enhanced the invasive ability. Numerous members of the MMP family are downstream             effectors of the Wnt/LEF1 pathway. Target prediction databases and luciferase             data showed that LEF1 is a new direct target of miR-218. Importantly, western             blot 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 reduced             synthesis of MMP-9. Results suggest that miR-218 is involved in the invasive behavior             of GBM cells and by targeting LEF1 and blocking the invasive axis, miR-218-LEF1-MMPs,             it may be useful for developing potential clinical strategies.
authors: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, PR China.
authors: Yanwei
authors: Y
authors: Liu
authors: Wei
authors: W
authors: Yan
authors: Wei
authors: W
authors: Zhang
authors: Lingchao
authors: L
authors: Chen
authors: Gan
authors: G
authors: You
authors: Zhaoshi
authors: Z
authors: Bao
authors: Yongzhi
authors: Y
authors: Wang
authors: Hongjun
authors: H
authors: Wang
authors: Chunsheng
authors: C
authors: Kang
authors: Tao
authors: T
authors: Jiang
mesh_terms: D001483:Base Sequence; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics* / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D046888:Tissue Array Analysis
chemical_list: C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9