MicroRNA-129-1 acts as tumour suppressor and induces cell cycle arrest of GBM cancer cells through targeting IGF2BP3 and MAPK1.
BACKGROUND
MicroRNA-129-1 (miR-129-1) seems to behave as a tumour suppressor since its decreased expression is associated with different tumours such as glioblastoma multiforme (GBM). GBM is the most common form of brain tumours originating from glial cells. The impact of miR-129-1 downregulation on GBM pathogenesis has yet to be elucidated.


METHODS
MiR-129-1 was overexpressed in GBM cells, and its effect on proliferation was investigated by cell cycle assay. MiR-129-1 predicted targets (CDK6, IGF1, HDAC2, IGF2BP3 and MAPK1) were also evaluated by western blot and luciferase assay.


RESULTS
Restoration of miR-129-1 reduced cell proliferation and induced G1 accumulation, significantly. Several functional assays confirmed IGF2BP3, MAPK1 and CDK6 as targets of miR-129-1. Despite the fact that IGF1 expression can be suppressed by miR-129-1, through 3'-untranslated region complementary sequence, we could not find any association between IGF1 expression and GBM. MiR-129-1 expression inversely correlates with CDK6, IGF2BP3 and MAPK1 in primary clinical samples.


CONCLUSIONS
This is the first study to propose miR129-1 as a negative regulator of IGF2BP3 and MAPK1 and also a cell cycle arrest inducer in GBM cells. Our data suggests miR-129-1 as a potential tumour suppressor and presents a rationale for the use of miR-129-1 as a novel strategy to improve treatment response in GBM.
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.
Fatemeh
F
Kouhkan
Metabolic Disorders Research Center, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Naser
N
Mobarra
Department of Hematology, School of Medicine, Tarbiat Modares University, Tehran, Iran.
Mina
M
Soufi-Zomorrod
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.
Farid
F
Keramati
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.
Seyed Mohammad Ali
SM
Hosseini Rad
National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Mehrnoosh
M
Fathi-Roudsari
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.
Rezvan
R
Tavakoli
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.
Athena
A
Hajarizadeh
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Said
S
Ziaei
Department of Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California, USA.
Reyhaneh
R
Lahmi
Department of Neurosurgery, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Hamed
H
Hanif
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran Department of Hematology, School of Medicine, Tarbiat Modares University, Tehran, Iran.
Masoud
M
Soleimani
D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D019295:Computational Biology; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics; D030541:Databases, Genetic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000235:genetics*; D008954:Models, Biological; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*
C498780:IGF2BP3 protein, human; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D007334:Insulin-Like Growth Factor I; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1
Cancer: CNS; Cell biology; Gene therapy; MicroRNA; Neuro oncology