title: MicroRNA miR-451 downregulates the PI3K/AKT pathway through CAB39 in             human glioma.
abstract: The microRNA miR-451 is downregulated in gliomas, this has been suggested by several different research groups and is consistent with our data. Our previous study also confirmed that miR-451 has a repressive role in glioma by inhibiting cell growth, proliferation and by inducing cell apoptosis. In the present study, we identified a target gene of miR-451 in human glioma and investigated the mechanism for the glioma suppressive effect of miR-451 functions. Expression of miR-451 in gliomas was identified by quantitative real-time PCR and fluorescence in situ hybridization. Human glioma cell lines (U251, U87, LN229 and A172) were transfected with miR-451 mimics to restore miR-451 expression. The tumor suppressive effects of miR-451 were further verified by subcutaneous assays in nude mice, in addition to our previous in vitro data. A candidate target gene was tested by Western blotting and luciferase reporter assays. Some PI3K/AKT pathway factors were tested by Western blotting. We found that miR-451 expression was downregulated in glioma samples and was inversely correlated with WHO grades of gliomas. In vivo assays confirmed that miR-451 had tumor suppressive traits. CAB39-3'UTR luciferase reporter assay confirmed CAB39 as a direct target gene of miR-451. Significant alterations in the expression of PI3K/AKT pathway factors were observed by Western blot assays. We conclude that miR-451 represses glioma in vitro and in vivo, likely through targeting CAB39 directly and inhibiting the PI3K/AKT pathway indirectly.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Yang
authors.initials: Y
authors.lastname: Nan
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Anling
authors.initials: A
authors.lastname: Zhang
authors.forename: Guangxiu
authors.initials: G
authors.lastname: Wang
authors.forename: Zhifan
authors.initials: Z
authors.lastname: Jia
authors.forename: Jianwei
authors.initials: J
authors.lastname: Hao
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhong
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D002135:Calcium-Binding Proteins; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C540569:CAB39 protein, human; C531201:MIRN451 microRNA, human