Skip to main content
Top
Published in: Tumor Biology 12/2015

01-12-2015 | Research Article

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

Authors: Fulin Xu, Feng Li, Weifeng Zhang, Pifeng Jia

Published in: Tumor Biology | Issue 12/2015

Login to get access

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.
Literature
1.
2.
go back to reference Chen J, Huang Q, Wang F. Inhibition of foxo1 nuclear exclusion prevents metastasis of glioblastoma. Tumour Biol. 2014;35:7195–200.CrossRefPubMed Chen J, Huang Q, Wang F. Inhibition of foxo1 nuclear exclusion prevents metastasis of glioblastoma. Tumour Biol. 2014;35:7195–200.CrossRefPubMed
3.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference Yu Y, Ran Q. Nuclear SMAD2 restrains proliferation of glioblastoma. Cell Physiol Biochem. 2015;35:1756–63.CrossRefPubMed Yu Y, Ran Q. Nuclear SMAD2 restrains proliferation of glioblastoma. Cell Physiol Biochem. 2015;35:1756–63.CrossRefPubMed
6.
go back to reference Gong J, Zhu S, Zhang Y, Wang J. Interplay of VEGFa and MMP2 regulates invasion of glioblastoma. Tumour Biol. 2014;35:11879–85.CrossRefPubMed Gong J, Zhu S, Zhang Y, Wang J. Interplay of VEGFa and MMP2 regulates invasion of glioblastoma. Tumour Biol. 2014;35:11879–85.CrossRefPubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CM. Delivering the promise of mirna cancer therapeutics. Drug Discov Today. 2013;18:282–9.CrossRefPubMed Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CM. Delivering the promise of mirna cancer therapeutics. Drug Discov Today. 2013;18:282–9.CrossRefPubMed
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference Li S, Guo W, Gao Y, Liu Y. Ginsenoside Rh2 inhibits growth of glioblastoma multiforme through mTor. Tumour Biol. 2015;36:2607–12.CrossRefPubMed Li S, Guo W, Gao Y, Liu Y. Ginsenoside Rh2 inhibits growth of glioblastoma multiforme through mTor. Tumour Biol. 2015;36:2607–12.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference John B, Sander C, Marks DS. Prediction of human microrna targets. Methods Mol Biol. 2006;342:101–13.PubMed John B, Sander C, Marks DS. Prediction of human microrna targets. Methods Mol Biol. 2006;342:101–13.PubMed
19.
go back to reference Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microrna targets. Cell. 2003;115:787–98.CrossRefPubMed Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microrna targets. Cell. 2003;115:787–98.CrossRefPubMed
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference 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.PubMed 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.PubMed
24.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
Growth of glioblastoma is inhibited by miR-133-mediated EGFR suppression
Authors
Fulin Xu
Feng Li
Weifeng Zhang
Pifeng Jia
Publication date
01-12-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 12/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3724-4

Other articles of this Issue 12/2015

Tumor Biology 12/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine