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Tumor Biology

, Volume 36, Issue 12, pp 9553–9558 | Cite as

Growth of glioblastoma is inhibited by miR-133-mediated EGFR suppression

Research Article

Abstract

Glioblastoma multiforme (GBM) is a severe and highly lethal brain cancer, which malignancy largely stems from its growing in a relatively restrained area in the brain. Hence, the understanding of the molecular regulation of the growth of GBM is critical for improving its treatment. Dysregulation of microRNAs (miRNAs) has recently been shown to contribute to the development of GBM, whereas the role of miR-133 in GBM is unknown. Here, by qualitative reverse transcription polymerase chain reaction (RT-qPCR), we detected lower miR-133 levels in GBM tissues, compared to the paired normal brain tissue. We overexpressed or inhibited miR-133 in GBM cells. Cell growth and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. We found that overexpression of miR-133 decreased GBM cell growth and increased cell apoptosis, while depletion of miR-133 increased cell growth and decreased cell apoptosis. Bioinformatic analysis was performed, showing that miR-133 may target the 3′-untranslated region (3′-UTR) of the epidermal growth factor receptor (EGFR) that transduces cell growth signals. Further, the protein translation inhibition of EGFR by miR-133 was confirmed by a dual luciferase reporter assay. Together, these data suggest that reduced miR-133 levels in GBM tissues promotes cell growth and decreases cell apoptosis, possibly through targeting mRNA of EGFR to suppress its translation.

Keywords

Glioblastoma multiforme (GBM) miR-133 microRNAs (miRNA) Growth Epidermal growth factor receptor (EGFR) 

Notes

Conflicts of interest

None

References

  1. 1.
    Schonberg DL, Bao S, Rich JN. Genomics informs glioblastoma biology. Nat Genet. 2013;45:1105–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Chen J, Huang Q, Wang F. Inhibition of foxo1 nuclear exclusion prevents metastasis of glioblastoma. Tumour Biol. 2014;35:7195–200.CrossRefPubMedGoogle Scholar
  3. 3.
    Li S, Gao Y, Ma W, Guo W, Zhou G, Cheng T, et al. Egfr signaling-dependent inhibition of glioblastoma growth by ginsenoside rh2. Tumour Biol. 2014;35:5593–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Wang F, Xiao W, Sun J, Han D, Zhu Y. MiRNA-181c inhibits EGFR-signaling-dependent MMP9 activation via suppressing Akt phosphorylation in glioblastoma. Tumour Biol. 2014;35:8653–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Yu Y, Ran Q. Nuclear SMAD2 restrains proliferation of glioblastoma. Cell Physiol Biochem. 2015;35:1756–63.CrossRefPubMedGoogle Scholar
  6. 6.
    Gong J, Zhu S, Zhang Y, Wang J. Interplay of VEGFa and MMP2 regulates invasion of glioblastoma. Tumour Biol. 2014;35:11879–85.CrossRefPubMedGoogle Scholar
  7. 7.
    Yu X, Jiang Y, Wei W, Cong P, Ding Y, Xiang L, et al. Androgen receptor signaling regulates growth of glioblastoma multiforme in men. Tumour Biol. 2015;36:967–72.CrossRefPubMedGoogle Scholar
  8. 8.
    Di Leva G, Croce CM. Mirna profiling of cancer. Curr Opin Genet Dev. 2013;23:3–11.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CM. Delivering the promise of mirna cancer therapeutics. Drug Discov Today. 2013;18:282–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Liu Z, Liu Y, Li L, Xu Z, Bi B, Wang Y, et al. MiR-7-5p is frequently downregulated in glioblastoma microvasculature and inhibits vascular endothelial cell proliferation by targeting RAF1. Tumour Biol. 2014;35:10177–84.CrossRefPubMedGoogle Scholar
  11. 11.
    Chen J, Fu X, Wan Y, Wang Z, Jiang D, Shi L. miR-125b inhibitor enhance the chemosensitivity of glioblastoma stem cells to temozolomide by targeting Bak1. Tumour Biol. 2014;35:6293–302.CrossRefPubMedGoogle Scholar
  12. 12.
    Tivnan A, Zhao J, Johns TG, Day BW, Stringer BW, Boyd AW, et al. The tumor suppressor microRNA, miR-124a, is regulated by epigenetic silencing and by the transcriptional factor, rest in glioblastoma. Tumour Biol. 2014;35:1459–65.CrossRefPubMedGoogle Scholar
  13. 13.
    England B, Huang T, Karsy M. Current understanding of the role and targeting of tumor suppressor p53 in glioblastoma multiforme. Tumour Biol. 2013;34:2063–74.CrossRefPubMedGoogle Scholar
  14. 14.
    Li S, Guo W, Gao Y, Liu Y. Ginsenoside Rh2 inhibits growth of glioblastoma multiforme through mTor. Tumour Biol. 2015;36:2607–12.CrossRefPubMedGoogle Scholar
  15. 15.
    Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H, et al. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst. 1973;51:1417–23.CrossRefPubMedGoogle Scholar
  16. 16.
    John B, Sander C, Marks DS. Prediction of human microrna targets. Methods Mol Biol. 2006;342:101–13.PubMedGoogle Scholar
  17. 17.
    John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human microrna targets. PLoS Biol. 2004;2, e363.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Coronnello C, Benos PV. ComiR: combinatorial microRNA target prediction tool. Nucleic Acids Res. 2013;41:W159–64.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microrna targets. Cell. 2003;115:787–98.CrossRefPubMedGoogle Scholar
  20. 20.
    Megraw M, Sethupathy P, Corda B, Hatzigeorgiou AG. MiRGen: a database for the study of animal microRNA genomic organization and function. Nucleic Acids Res. 2007;35:D149–55.CrossRefPubMedGoogle Scholar
  21. 21.
    Alexiou P, Vergoulis T, Gleditzsch M, Prekas G, Dalamagas T, Megraw M, et al. MiRGen 2.0: a database of microRNA genomic information and regulation. Nucleic Acids Res. 2010;38:D137–41.CrossRefPubMedGoogle Scholar
  22. 22.
    Zhou Y, Wu D, Tao J, Qu P, Zhou Z, Hou J. MicroRNA-133 inhibits cell proliferation, migration and invasion by targeting epidermal growth factor receptor and its downstream effector proteins in bladder cancer. Scand J Urol. 2013;47:423–32.CrossRefPubMedGoogle Scholar
  23. 23.
    Tao J, Wu D, Xu B, Qian W, Li P, Lu Q, et al. MicroRNA-133 inhibits cell proliferation, migration and invasion in prostate cancer cells by targeting the epidermal growth factor receptor. Oncol Rep. 2012;27:1967–75.PubMedGoogle Scholar
  24. 24.
    Dong Y, Zhao J, Wu CW, Zhang L, Liu X, Kang W, et al. Tumor suppressor functions of miR-133a in colorectal cancer. Mol Cancer Res. 2013;11:1051–60.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Neurosurgery, Minhang HospitalFudan UniversityShanghaiChina
  2. 2.Department of Neurosurgery, Ruijin Hospital NorthShanghai Jiao Tong University School of MedicineShanghaiChina

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