title: MiRNA-451 plays a role as tumor suppressor in human glioma cells.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level by binding loosely complimentary sequences in the 3'untranslated regions (UTRs) of target mRNAs. Increased expressions of several miRNAs, specifically hsa-miR-21, have been reported to modulate glioma development. Here we report downregulation of miR-451 in A172, LN229 and U251 human glioblastoma cells. Increased expression of miR-451 by administration of miR-451 mimics oligonucleotides reversed the biology of each of the three cell lines, inhibiting cell growth, inducing G0/G1 phase arrest and increasing cell apoptosis. Further, treatment with miR-451 mimics oligonucleotides diminished the invasive capacity of these cells, as the number of cells invading through matrigel was significantly decreased. Akt1, CyclinD1, MMP-2, MMP-9 and Bcl-2 protein expression decreased, and p27 expression increased in a dose-dependent manner with miR-451 mimics oligonucleotides. Taken together, these studies reveal miR-451 impacts glioblastoma cell proliferation, invasion and apoptosis, perhaps via regulation of the PI3K/AKT signaling pathway. We propose an essential role for miR-451 as a tumor-suppressor of human glioma.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, People's Republic of China.
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: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiao
authors.initials: X
authors.lastname: Yue
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: D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053492:Elafin / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation
chemical_list: D053492:Elafin; D035683:MicroRNAs; C506806:PI3 protein, human; D051057:Proto-Oncogene Proteins c-akt