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Cited by 614MicroRNA in disease regulationGlioma Diagnosis and TreatmentCancer-related molecular mechanisms research

MicroRNA-34a Inhibits Glioblastoma Growth by Targeting Multiple Oncogenes

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Li, Yunqing, Guessous, Fadila, Zhang, Ying, DiPierro, Charles, Kefas, Benjamin, Johnson, Elizabeth, Marcinkiewicz, Lukasz, Jiang, Jinmai +6 more·2009·Cancer Research
DOI 10.1158/0008-5472.can-09-0529PMC PMC2756313
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Abstract

MicroRNA-34a (miR-34a) is a transcriptional target of p53 that is down-regulated in some cancer cell lines. We studied the expression, targets, and functional effects of miR-34a in brain tumor cells and human gliomas. Transfection of miR-34a down-regulated c-Met in human glioma and medulloblastoma cells and Notch-1, Notch-2, and CDK6 protein expressions in glioma cells. miR-34a expression inhibited c-Met reporter activities in glioma and medulloblastoma cells and Notch-1 and Notch-2 3′-untranslated region reporter activities in glioma cells and stem cells. Analysis of human specimens showed that miR-34a expression is down-regulated in glioblastoma tissues as compared with normal brain and in mutant p53 gliomas as compared with wild-type p53 gliomas. miR-34a levels in human gliomas inversely correlated to c-Met levels measured in the same tumors. Transient transfection of miR-34a into glioma and medulloblastoma cell lines strongly inhibited cell proliferation, cell cycle progression, cell survival, and cell invasion, but transfection of miR-34a into human astrocytes did not affect cell survival and cell cycle status. Forced expression of c-Met or Notch-1/Notch-2 transcripts lacking the 3′-untranslated region sequences partially reversed the effects of miR-34a on cell cycle arrest and cell death in glioma cells and stem cells, respectively. Also, transient expression of miR-34a in glioblastoma cells strongly inhibited in vivo glioma xenograft growth. Together, these findings represent the first comprehensive analysis of the role of miR-34a in gliomas. They show that miR-34a suppresses brain tumor growth by targeting c-Met and Notch. The results also suggest that miR-34a could serve as a potential therapeutic agent for brain tumors. [Cancer Res 2009;69(19):7569–76]

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  • Mir-34a is a transcriptional target of p53 and is commonly downregulated in glioblastoma, and negatively affects glioblastoma cell proliferation, invasion, cell survival, and cell cycle progression.

    “Mir-34a is as a transcriptional target of p53 and is commonly downregulated in GBM, and negatively affects GBM cell proliferation, invasion, cell survival, and cell cycle progression [51].”

    From The p53 Pathway in Glioblastoma (2018) · cites this paper as [51]

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  1. [1]Li Y Lal B Kwon S The scatter factor/hepatocyte growth factor: c-met pathway in human embryonal central nervous system tumor malignancy Cancer Res 2005 65 9355 62 16230398
  2. [2]Laterra J Nam M Rosen E Rao JS Johnston P Scatter factor/hepatocyte growth factor gene transfer to 9L glioma cells enhances glioma growth and angiogenesis in vivo Lab Invest 1997 76 565 77 9111517
  3. [3]Abounader R Ranganathan S Lal B Reversion of human glioblastoma malignancy by U1 small nuclear RNA/ribozyme targeting of scatter factor/hepatocyte growth factor and c- met expression J Natl Cancer Inst 1999 91 1548 56 10491431
  4. [4]Rosen EM Laterra J Joseph A Scatter factor expression and regulation in human glial tumors Intl J Cancer 1996 67 248 55 8760595
  5. [5]Moriyama T Kataoka H Kawano Y Comparative analysis of expression of hepatocyte growth factor and its receptor, c-met, in gliomas, meningiomas and schwannomas Canc Lett 1998 124 149 55 9500204
  6. [6]Koochekpour S Jeffers M Rulong S Met and hepatocyte growth factor/scatter factor expression in human gliomas Cancer Res 1997 57 5391 8 9393765
  7. [7]Abounader R Laterra J Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis Neuro-oncol 2005 7 436 51 16212809 PMC1871724
  8. [8]Purow BW Haque RM Noel MW Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation Cancer Res 2005 65 2353 63 15781650
  9. [9]Purow BW Sundaresan TK Burdick MJ Notch-1 regulates transcription of the epidermal growth factor receptor through p53 Carcinogenesis 2008 29 918 25 18359760 PMC2902388
  10. [10]Fan X Matsui W Khaki L Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors Cancer Res 2006 66 7445 52 16885340
  11. [11]Shih AH Holland EC Notch signaling enhances nestin expression in gliomas Neoplasia 2006 8 1072 82 17217625 PMC1790729
  12. [12]Kanamori M Kawaguchi T Nigro JM Contribution of Notch signaling activation to human glioblastoma multiforme J Neurosurg 2007 106 417 27 17367064
  13. [13]Mendrzyk F Radlwimmer B Joos S Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma J Clin Oncol 2005 23 8853 62 16314645
  14. [14]Lam PY Di Tomaso E Ng HK Pang JC Roussel MF Hjelm NM Expression of p19INK4d, CDK4, CDK6 in glioblastoma multiforme Br J Neurosurg 2000 14 28 32 10884881
  15. [15]Pierson J Hostager B Fan R Vibhakar R Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma J Neurooncol 2008 90 1 7 18607543
  16. [16]Ambros V Lee RC Identification of microRNAs and other tiny noncoding RNAs by cDNA cloning Methods Mol Biol 2004 265 131 58 15103073
  17. [17]Pillai RS Bhattacharyya SN Filipowicz W Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol 2007 17 118 26 17197185
  18. [18]Caldas C Brenton JD Sizing up miRNAs as cancer genes Nat Med 2005 11 712 4 16015356
  19. [19]Calin GA Croce CM MicroRNA signatures in human cancers Nat Rev Cancer 2006 6 857 66 17060945
  20. [20]Kefas B Godlewski J Comeau L microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma Cancer Res 2008 68 3566 72 18483236
  21. [21]Gaur A Jewell DA Liang Y Characterization of microRNA expression levels and their biological correlates in human cancer cell lines Cancer Res 2007 67 2456 68 17363563
  22. [23]Raver-Shapira N Marciano E Meiri E Transcriptional activation of miR-34a contributes to p53-mediated apoptosis Mol Cell 2007 26 731 43 17540598
  23. [24]Tarasov V Jung P Verdoodt B Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest Cell Cycle 2007 6 1586 93 17554199
  24. [25]He L He X Lim LP A microRNA component of the p53 tumour suppressor network Nature 2007 447 1130 4 17554337 PMC4590999
  25. [26]Li N Fu H Tie Y miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells Cancer Lett 2008 19006648
  26. [27]Yan D Zhou X Chen X MicroRNA-34a Inhibits Uveal Melanoma Cell Proliferation and Migration through Downregulation of c-Met Invest Ophthalmol Vis Sci 2008 19029026
  27. [28]Li Y Guessous F Johnson EB Functional and molecular interactions between the HGF/c-Met pathway and c-Myc in large-cell medulloblastoma Lab Invest 2008 88 98 111 18059365
  28. [30]Welch C Chen Y Stallings RL MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells Oncogene 2007 26 5017 22 17297439
  29. [31]Tazawa H Tsuchiya N Izumiya M Nakagama H Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells Proc Natl Acad Sci U S A 2007 104 15472 7 17875987 PMC2000550
  30. [32]Lodygin D Tarasov V Epanchintsev A Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer Cell Cycle 2008 7 2591 600 18719384
  31. [33]Barbashina V Salazar P Holland EC Rosenblum MK Ladanyi M Allelic losses at 1p36 and 19q13 in gliomas: correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene Clin Cancer Res 2005 11 1119 28 15709179
  32. [34]Wei JS Song YK Durinck S The MYCN oncogene is a direct target of miR-34a Oncogene 2008 27 5204 13 18504438 PMC2562938
  33. [35]Louis DN The p53 gene and protein in human brain tumors J Neuropathol Exp Neurol 1994 53 11 21 8301315
  34. [36]Zupanska A Kaminska B The diversity of p53 mutations among human brain tumors and their functional consequences Neurochem Int 2002 40 637 45 11900859
  35. [37]Fan X Mikolaenko I Elhassan I Notch1 and notch2 have opposite effects on embryonal brain tumor growth Cancer Res 2004 64 7787 93 15520184
  36. [38]Sun F Fu H Liu Q Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest FEBS Lett 2008 582 1564 8 18406353
  37. [39]Cole KA Attiyeh EF Mosse YP A functional screen identifies miR-34a as a candidate neuroblastoma tumor suppressor gene Mol Cancer Res 2008 6 735 42 18505919 PMC3760152
  38. [40]Yamakuchi M Ferlito M Lowenstein CJ miR-34a repression of SIRT1 regulates apoptosis Proc Natl Acad Sci U S A 2008 105 13421 6 18755897 PMC2533205

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Authors
Li, Y., Guessous, F., Zhang, Y., DiPierro, C., Kefas, B., Johnson, E., Marcinkiewicz, L., Jiang, J., Yang, Y., Schmittgen, T. D., Lopes, B., Schiff, D., Purow, B., & Abounader, R.
Affiliations
  • 1Microbiology, Departments of
  • University of Virginia (US)
  • 2Neurology and
  • The Ohio State University (US)
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2009-10-01
Volume
69
Issue
19
Pages
7569-7576
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-09-0529
PMC
PMC2756313
OpenAlex
W2093364931
Cited by
614
References
2
Citations by year
2026: 13 · 2025: 11 · 2024: 13 · 2023: 18 · 2022: 20 · 2021: 30 · 2020: 27 · 2019: 28 · 2018: 30 · 2017: 43 · 2016: 47 · 2015: 51 · 2014: 61 · 2013: 66 · 2012: 59
FWCI
17.34
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • UVA Cancer Center
  • National Institutes of Health
  • National Cancer Institute (R01CA134843)
  • National Institute of Neurological Disorders and Stroke (R01NS045209)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
miR-34a, glioblastoma, glioma, medulloblastoma, c-Met, Notch1, Notch2, CDK6, p53, 3' untranslated region, tumor suppressor microRNA, cell cycle arrest, cell invasion, brain tumor therapy, xenograft tumor growth
MeSH terms
Brain Neoplasms, Cell Cycle, Glioblastoma, Humans, Oncogenes, Transfection, Genetic Therapy, Down-Regulation, Proto-Oncogene Proteins c-met, 3' Untranslated Regions, Receptor, Platelet-Derived Growth Factor alpha, MicroRNAs, Cyclin-Dependent Kinase 6, Receptor, Notch1, Receptor, Notch2

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