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Microrna-129-1 Acts As Tumour Suppressor and Induces Cell Cycle Arrest of Gbm Cancer Cells Through Targeting Igf2bp3 and Mapk1 Publisher Pubmed



Kouhkan F1 ; Mobarra N2 ; Soufizomorrod M3 ; Keramati F1 ; Ali Hosseini Rad SM1 ; Fathiroudsari M4 ; Tavakoli R1 ; Hajarizadeh A1 ; Ziaei S1, 5 ; Lahmi R6 ; Hanif H7 ; Soleimani M1, 3
Authors
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Authors Affiliations
  1. 1. Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran
  2. 2. Metabolic Disorders Research Center, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
  3. 3. Department of Hematology, School of Medicine, Tarbiat Modares University, P.O. Box:14115-331, Tehran, Iran
  4. 4. National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
  5. 5. Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  6. 6. Department of Neuroscience, Aging and Stem Cell Research Center, Sanford- Burnham Medical Research Institute, La Jolla, CA, United States
  7. 7. Department of Neurosurgery, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Medical Genetics Published:2015


Abstract

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 30-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. Conclusion 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.
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