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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

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Cancer genetics
Original article
MicroRNA-129-1 acts as tumour suppressor and induces cell cycle arrest of GBM cancer cells through targeting IGF2BP3 and MAPK1
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  1. Fatemeh Kouhkan1,
  2. Naser Mobarra2,
  3. Mina Soufi-Zomorrod3,
  4. Farid Keramati1,
  5. Seyed Mohammad Ali Hosseini Rad1,
  6. Mehrnoosh Fathi-Roudsari4,
  7. Rezvan Tavakoli1,
  8. Athena Hajarizadeh1,
  9. Said Ziaei1,5,
  10. Reyhaneh Lahmi6,
  11. Hamed Hanif7,
  12. Masoud Soleimani1,3
  1. 1Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran
  2. 2Metabolic Disorders Research Center, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
  3. 3Department of Hematology, School of Medicine, Tarbiat Modares University, Tehran, Iran
  4. 4National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
  5. 5Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  6. 6Department of Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California, USA
  7. 7Department of Neurosurgery, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  1. Correspondence to Fatemeh Kouhkan, Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, P.O. Box: 15856-36473, Tehran 15856-36473, Iran; f.kouhkan{at}stemcellstech.com, f.kouhkan{at}yahoo.com Masoud Soleimani Department of Hematology, School of Medical Sciences, Tarbiat Modares University, P.O. Box:14115-331, Tehran, Iran; soleim_m@modares.ac.ir

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 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.

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.

  • Cancer: CNS
  • Cell biology
  • Gene therapy
  • MicroRNA
  • Neuro oncology

https://doi.org/10.1136/jmedgenet-2015-103225

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