title: Identification of MMP-9 specific microRNA expression profile as potential targets of anti-invasion therapy in glioblastoma multiforme.
abstract: The poor prognosis of glioblastoma multiforme (GBM) is largely attributed to their highly invasive nature and MMP-9 plays a pivotal role in regulating invasiveness of malignant glioma cells. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to regulate a wide range of biological processes via targeting messenger RNA. Previous reports have shown many oncogenes regulate survival and invasion via targeting MMP-9 in GBM. But no literature indicates that miRNAs regulate glioma cell invasion through targeting MMP-9. Here, we show MMP-9 overexpression conferred a poor prognosis in 163 GBM patients. Furthermore, MMP-9 specific miRNA expression profile (14 positively and 31 negatively correlated miRNAs with MMP-9) was established via miRNA microarrays in 60 GBM samples. Among them, two miRNAs: miR-885-5p and miR-491-5p, were chosen for functional validation for their high positive correlation with MMP-9 expression. And upregulation of miR-885-5p and miR-491-5p were demonstrated to reduce the levels of MMP-9 expression and inhibit cellular invasion in U251 and U87 glioma cells. Furthermore, we found that miR-491-5p suppressed glioma cell invasion via targeting MMP-9 directly. To our knowledge, this is the first study to identify the MMP-9 specific microRNA signature which may provide potential targets for anti-invasion therapy in GBM.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, No.6 Tiantan Xili, Dongcheng District, Beijing 100050, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Liu
authors.forename: Gan
authors.initials: G
authors.lastname: You
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D015536:Down-Regulation / Q000187:drug effects; D017930:Genes, Reporter; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008156:Luciferases / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009841:Oligonucleotides / Q000235:genetics; D011379:Prognosis; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000302:isolation & purification; D016019:Survival Analysis; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D009841:Oligonucleotides; D012334:RNA, Neoplasm; D008156:Luciferases; D020780:Matrix Metalloproteinase 9