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MicroRNAs as Regulators of Neural Stem Cell-Related Pathways in Glioblastoma Multiforme

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Abstract

MicroRNAs are endogenous non-coding small RNAs that have been described as highly conserved regulators of gene expression. They are involved in cancer and in the regulation of neural development and stem cell function. Recent studies suggest that a small subpopulation of cancer stem cells (CSCs) has the capacity to repopulate solid tumours such as glioblastoma (GBM), drive malignant progression and mediate radio- and chemoresistance. GBM-derived CSCs share the fundamental stem cell properties of self-renewal and multipotency with neural stem cells (NSCs) and may be regulated by miRNAs. In this review, we will summarize the current knowledge regarding the role of miRNAs in GBM development with a focus on the regulation of GBM-CSCs. We propose a list of miRNAs that could serve as molecular classifiers for GBMs and/or as promising therapeutic targets for such brain tumours.

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References

  1. Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A et al (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21:2683–2710

    PubMed  CAS  Google Scholar 

  2. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    PubMed  Google Scholar 

  3. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD et al (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157–173

    PubMed  CAS  Google Scholar 

  4. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110

    PubMed  CAS  Google Scholar 

  5. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111

    PubMed  CAS  Google Scholar 

  6. Read TA, Hegedus B, Wechsler-Reya R, Gutmann DH (2006) The neurobiology of neurooncology. Ann Neurol 60:3–11

    PubMed  CAS  Google Scholar 

  7. Zaidi HA, Kosztowski T, DiMeco F, Quinones-Hinojosa A (2009) Origins and clinical implications of the brain tumor stem cell hypothesis. J Neurooncol 93:49–60

    PubMed  Google Scholar 

  8. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al (2004) Identification of human brain tumour initiating cells. Nature 432:396–401

    PubMed  CAS  Google Scholar 

  9. Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S et al (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021

    PubMed  CAS  Google Scholar 

  10. Mazzoleni S, Politi LS, Pala M, Cominelli M, Franzin A, Sergi SL et al (2010) Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis. Cancer Res 70:7500–7513

    PubMed  CAS  Google Scholar 

  11. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760

    PubMed  CAS  Google Scholar 

  12. Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G et al (2006) Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444:761–765

    PubMed  CAS  Google Scholar 

  13. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Altaba A (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 17:165–172

    PubMed  CAS  Google Scholar 

  14. Stockhausen MT, Kristoffersen K, Poulsen HS (2010) The functional role of Notch signaling in human gliomas. Neuro Oncol 12(2):199–211

    PubMed  CAS  Google Scholar 

  15. Li Z, Wang H, Eyler CE, Hjelmeland AB, Rich JN (2009) Turning cancer stem cells inside out: an exploration of glioma stem cell signaling pathways. J Biol Chem 284:16705–16709

    PubMed  CAS  Google Scholar 

  16. Ohgaki H, Kleihues P (2007) Genetic pathways to primary and secondary glioblastoma. Am J Pathol 170:1445–1453

    PubMed  CAS  Google Scholar 

  17. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812

    PubMed  CAS  Google Scholar 

  18. Soeda A, Inagaki A, Oka N, Ikegame Y, Aoki H, Yoshimura S et al (2008) Epidermal growth factor plays a crucial role in mitogenic regulation of human brain tumor stem cells. J Biol Chem 283:10958–10966

    PubMed  CAS  Google Scholar 

  19. Ciccolini F, Mandl C, Holzl-Wenig G, Kehlenbach A, Hellwig A (2005) Prospective isolation of late development multipotent precursors whose migration is promoted by EGFR. Dev Biol 284:112–125

    PubMed  CAS  Google Scholar 

  20. Pastrana E, Cheng LC, Doetsch F (2009) Simultaneous prospective purification of adult subventricular zone neural stem cells and their progeny. Proc Natl Acad Sci U S A 106:6387–6392

    PubMed  CAS  Google Scholar 

  21. Li L, Dutra A, Pak E, Labrie JE III, Gerstein RM, Pandolfi PP et al (2009) EGFRvIII expression and PTEN loss synergistically induce chromosomal instability and glial tumors. Neuro Oncol 11:9–21

    PubMed  Google Scholar 

  22. Griffero F, Daga A, Marubbi D, Capra MC, Melotti A, Pattarozzi A et al (2009) Different response of human glioma tumor-initiating cells to epidermal growth factor receptor kinase inhibitors. J Biol Chem 284:7138–7148

    PubMed  CAS  Google Scholar 

  23. Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, Roy M, Quinones-Hinojosa A, VandenBerg S et al (2006) PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron 51:187–199

    PubMed  CAS  Google Scholar 

  24. Liu KW, Feng H, Bachoo R, Kazlauskas A, Smith EM, Symes K et al (2011) SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and INK4A/ARF aberrations in mice and humans. J Clin Invest 43690

  25. Gil-Perotin S, Marin-Husstege M, Li J, Soriano-Navarro M, Zindy F, Roussel MF et al (2006) Loss of p53 induces changes in the behavior of subventricular zone cells: implication for the genesis of glial tumors. J Neurosci 26:1107–1116

    PubMed  CAS  Google Scholar 

  26. Meletis K, Wirta V, Hede SM, Nister M, Lundeberg J, Frisen J (2006) p53 suppresses the self-renewal of adult neural stem cells. Development 133:363–369

    PubMed  CAS  Google Scholar 

  27. Ferron SR, Marques-Torrejon MA, Mira H, Flores I, Taylor K, Blasco MA et al (2009) Telomere shortening in neural stem cells disrupts neuronal differentiation and neuritogenesis. J Neurosci 29:14394–14407

    PubMed  CAS  Google Scholar 

  28. Wang Y, Yang J, Zheng H, Tomasek GJ, Zhang P, McKeever PE et al (2009) Expression of mutant p53 proteins implicates a lineage relationship between neural stem cells and malignant astrocytic glioma in a murine model. Cancer Cell 15:514–526

    PubMed  CAS  Google Scholar 

  29. Zheng H, Ying H, Yan H, Kimmelman AC, Hiller DJ, Chen AJ et al (2008) p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature 455:1129–1133

    PubMed  CAS  Google Scholar 

  30. Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425:962–967

    PubMed  CAS  Google Scholar 

  31. Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J et al (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448–452

    PubMed  CAS  Google Scholar 

  32. Kippin TE, Martens DJ, van der Kooy D (2005) p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity. Genes Dev 19:756–767

    PubMed  CAS  Google Scholar 

  33. MacNicol MC, Cragle CE, MacNicol AM (2011) Context-dependent regulation of Musashi-mediated mRNA translation and cell cycle regulation. Cell Cycle 10(1):39–44

    PubMed  CAS  Google Scholar 

  34. Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355

    PubMed  CAS  Google Scholar 

  35. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    PubMed  CAS  Google Scholar 

  36. Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6:376–385

    PubMed  CAS  Google Scholar 

  37. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D et al (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    PubMed  CAS  Google Scholar 

  38. Hammond SM (2006) MicroRNAs as oncogenes. Curr Opin Genet Dev 16:4–9

    PubMed  CAS  Google Scholar 

  39. Barbarotto E, Schmittgen TD, Calin GA (2008) MicroRNAs and cancer: profile, profile, profile. Int J Cancer 122:969–977

    PubMed  CAS  Google Scholar 

  40. Calin GA (2009) MicroRNAs and cancer: what we know and what we still have to learn. Genome Med 1:78

    PubMed  Google Scholar 

  41. Kim TM, Huang W, Park R, Park PJ, Johnson MD (2011) A developmental taxonomy of glioblastoma defined and maintained by microRNAs. Cancer Res

  42. Zhi F, Chen X, Wang S, Xia X, Shi Y, Guan W et al (2010) The use of hsa-miR-21, hsa-miR-181b and hsa-miR-106a as prognostic indicators of astrocytoma. Eur J Cancer 46:1640–1649

    PubMed  CAS  Google Scholar 

  43. Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033

    PubMed  CAS  Google Scholar 

  44. Zhou X, Zhang J, Jia Q, Ren Y, Wang Y, Shi L et al (2010) Reduction of miR-21 induces glioma cell apoptosis via activating caspase 9 and 3. Oncol Rep 24:195–201

    PubMed  CAS  Google Scholar 

  45. Chen Y, Liu W, Chao T, Zhang Y, Yan X, Gong Y et al (2008) MicroRNA-21 down-regulates the expression of tumor suppressor PDCD4 in human glioblastoma cell T98G. Cancer Lett 272:197–205

    PubMed  CAS  Google Scholar 

  46. Zhou X, Ren Y, Moore L, Mei M, You Y, Xu P et al (2010) Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. Lab Invest 90:144–155

    PubMed  CAS  Google Scholar 

  47. Ren Y, Zhou X, Mei M, Yuan XB, Han L, Wang GX et al (2010) MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol. BMC Cancer 10:2727

    Google Scholar 

  48. Papagiannakopoulos T, Shapiro A, Kosik KS (2008) MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res 68:8164–8172

    PubMed  CAS  Google Scholar 

  49. Gabriely G, Wurdinger T, Kesari S, Esau CC, Burchard J, Linsley PS et al (2008) MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol Cell Biol 28:5369–5380

    PubMed  CAS  Google Scholar 

  50. Kwak HJ, Kim YJ, Chun KR, Woo YM, Park SJ, Jeong JA et al (2011) Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas. Oncogene

  51. Corsten MF, Miranda R, Kasmieh R, Krichevsky AM, Weissleder R, Shah K (2007) MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. Cancer Res 67:8994–9000

    PubMed  CAS  Google Scholar 

  52. Ren Y, Kang CS, Yuan XB, Zhou X, Xu P, Han L et al (2010) Co-delivery of as-miR-21 and 5-FU by poly(amidoamine) dendrimer attenuates human glioma cell growth in vitro. J Biomater Sci Polym Ed 21:303–314

    PubMed  CAS  Google Scholar 

  53. Ren Y, Zhou X, Mei M, Yuan XB, Han L, Wang GX et al (2010) MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol. BMC Cancer 10:27

    PubMed  Google Scholar 

  54. Shi L, Chen J, Yang J, Pan T, Zhang S, Wang Z (2010) MiR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity. Brain Res 1352:255–264

    PubMed  CAS  Google Scholar 

  55. Li Y, Li W, Yang Y, Lu Y, He C, Hu G et al (2009) MicroRNA-21 targets LRRFIP1 and contributes to VM-26 resistance in glioblastoma multiforme. Brain Res 1286:13–18

    PubMed  CAS  Google Scholar 

  56. Conti A, Aguennouz M, La Torre D, Tomasello C, Cardali S, Angileri FF et al (2009) miR-21 and 221 upregulation and miR-181b downregulation in human grade II–IV astrocytic tumors. J Neurooncol 93:325–332

    PubMed  CAS  Google Scholar 

  57. Gillies JK, Lorimer IA (2007) Regulation of p27Kip1 by miRNA 221/222 in glioblastoma. Cell Cycle 6:2005–2009

    PubMed  CAS  Google Scholar 

  58. Zhang C, Kang C, You Y, Pu P, Yang W, Zhao P et al (2009) Co-suppression of miR-221/222 cluster suppresses human glioma cell growth by targeting p27kip1 in vitro and in vivo. Int J Oncol 34:1653–1660

    PubMed  CAS  Google Scholar 

  59. Medina R, Zaidi SK, Liu CG, Stein JL, van Wijnen AJ, Croce CM et al (2008) MicroRNAs 221 and 222 bypass quiescence and compromise cell survival. Cancer Res 68:2773–2780

    PubMed  CAS  Google Scholar 

  60. le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A et al (2007) Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J 26:3699–3708

    PubMed  Google Scholar 

  61. Zhang J, Han L, Ge Y, Zhou X, Zhang A, Zhang C et al (2010) miR-221/222 promote malignant progression of glioma through activation of the Akt pathway. Int J Oncol 36:913–920

    PubMed  CAS  Google Scholar 

  62. Huse JT, Brennan C, Hambardzumyan D, Wee B, Pena J, Rouhanifard SH et al (2009) The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo. Genes Dev 23:1327–1337

    PubMed  CAS  Google Scholar 

  63. Kim H, Huang W, Jiang X, Pennicooke B, Park PJ, Johnson MD (2010) Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship. Proc Natl Acad Sci U S A 107:2183–2188

    PubMed  CAS  Google Scholar 

  64. Kefas B, Godlewski J, Comeau L, Li Y, Abounader R, Hawkinson M et al (2008) microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. Cancer Res 68:3566–3572

    PubMed  CAS  Google Scholar 

  65. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5:R13

    PubMed  Google Scholar 

  66. Zhang Y, Chao T, Li R, Liu W, Chen Y, Yan X et al (2009) MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a. J Mol Med 87:43–51

    PubMed  CAS  Google Scholar 

  67. Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M et al (2008) miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med 6:14

    PubMed  Google Scholar 

  68. Godlewski J, Nowicki MO, Bronisz A, Williams S, Otsuki A, Nuovo G et al (2008) Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res 68:9125–9130

    PubMed  CAS  Google Scholar 

  69. Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G et al (2005) Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 334:1351–1358

    PubMed  CAS  Google Scholar 

  70. Cui JG, Zhao Y, Sethi P, Li YY, Mahta A, Culicchia F et al (2010) Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation. J Neurooncol 98:297–304

    PubMed  CAS  Google Scholar 

  71. Adlakha YK, Saini N (2010) MicroRNA-128 downregulates Bax and induces apoptosis in human embryonic kidney cells. Cell Mol Life Sci

  72. Itahana K, Zou Y, Itahana Y, Martinez JL, Beausejour C, Jacobs JJ et al (2003) Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1. Mol Cell Biol 23:389–401

    PubMed  CAS  Google Scholar 

  73. Venkataraman S, Alimova I, Fan R, Harris P, Foreman N, Vibhakar R (2010) MicroRNA 128a increases intracellular ROS level by targeting Bmi-1 and inhibits medulloblastoma cancer cell growth by promoting senescence. PLoS One 5:e10748

    PubMed  Google Scholar 

  74. Shi L, Cheng Z, Zhang J, Li R, Zhao P, Fu Z et al (2008) hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res 1236:185–193

    PubMed  CAS  Google Scholar 

  75. Slaby O, Lakomy R, Fadrus P, Hrstka R, Kren L, Lzicarova E et al (2010) MicroRNA-181 family predicts response to concomitant chemoradiotherapy with temozolomide in glioblastoma patients. Neoplasma 57:264–269

    PubMed  CAS  Google Scholar 

  76. Chen G, Zhu W, Shi D, Lv L, Zhang C, Liu P et al (2010) MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2. Oncol Rep 23:997–1003

    PubMed  CAS  Google Scholar 

  77. Wurdinger T, Tannous BA, Saydam O, Skog J, Grau S, Soutschek J et al (2008) miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell 14:382–393

    PubMed  CAS  Google Scholar 

  78. Chen C, Ridzon D, Lee CT, Blake J, Sun Y, Strauss WM (2007) Defining embryonic stem cell identity using differentiation-related microRNAs and their potential targets. Mamm Genome 18:316–27

    PubMed  CAS  Google Scholar 

  79. Houbaviy HB, Murray MF, Sharp PA (2003) Embryonic stem cell-specific MicroRNAs. Dev Cell 5:351–358

    PubMed  CAS  Google Scholar 

  80. Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY et al (2004) Human embryonic stem cells express a unique set of microRNAs. Dev Biol 270:488–498

    PubMed  CAS  Google Scholar 

  81. Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9:1274–1281

    PubMed  CAS  Google Scholar 

  82. Miska EA, Alvarez-Saavedra E, Townsend M, Yoshii A, Sestan N, Rakic P et al (2004) Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 5:R68

    PubMed  Google Scholar 

  83. Lavon I, Zrihan D, Granit A, Einstein O, Fainstein N, Cohen MA et al (2010) Gliomas display a microRNA expression profile reminiscent of neural precursor cells. Neuro Oncol 12:422–433

    PubMed  CAS  Google Scholar 

  84. Cao X, Pfaff SL, Gage FH (2007) A functional study of miR-124 in the developing neural tube. Genes Dev 21:531–536

    PubMed  CAS  Google Scholar 

  85. Makeyev EV, Zhang J, Carrasco MA, Maniatis T (2007) The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 27:435–448

    PubMed  CAS  Google Scholar 

  86. Cheng LC, Pastrana E, Tavazoie M, Doetsch F (2009) miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci 12:399–408

    PubMed  CAS  Google Scholar 

  87. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12:735–739

    PubMed  CAS  Google Scholar 

  88. Li KK, Pang JC, Ching AK, Wong CK, Kong X, Wang Y et al (2009) miR-124 is frequently down-regulated in medulloblastoma and is a negative regulator of SLC16A1. Hum Pathol 40:1234–1243

    PubMed  CAS  Google Scholar 

  89. Le MT, Xie H, Zhou B, Chia PH, Rizk P, Um M et al (2009) MicroRNA-125b promotes neuronal differentiation in human cells by repressing multiple targets. Mol Cell Biol 29:5290–5305

    PubMed  CAS  Google Scholar 

  90. Shi L, Zhang J, Pan T, Zhou J, Gong W, Liu N et al (2010) MiR-125b is critical for the suppression of human U251 glioma stem cell proliferation. Brain Res 1312:120–126

    PubMed  CAS  Google Scholar 

  91. Xia HF, He TZ, Liu CM, Cui Y, Song PP, Jin XH et al (2009) MiR-125b expression affects the proliferation and apoptosis of human glioma cells by targeting Bmf. Cell Physiol Biochem 23:347–358

    PubMed  CAS  Google Scholar 

  92. Gal H, Pandi G, Kanner AA, Ram Z, Lithwick-Yanai G, Amariglio N et al (2008) MIR-451 and Imatinib mesylate inhibit tumor growth of Glioblastoma stem cells. Biochem Biophys Res Commun 376:86–90

    PubMed  CAS  Google Scholar 

  93. Godlewski J, Bronisz A, Nowicki MO, Chiocca EA, Lawler S (2010) microRNA-451: a conditional switch controlling glioma cell proliferation and migration. Cell Cycle 9:2742–2748

    PubMed  CAS  Google Scholar 

  94. Godlewski J, Nowicki MO, Bronisz A, Nuovo G, Palatini J, De LM et al (2010) MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol Cell 37:620–632

    PubMed  CAS  Google Scholar 

  95. Nan Y, Han L, Zhang A, Wang G, Jia Z, Yang Y et al (2010) MiRNA-451 plays a role as tumor suppressor in human glioma cells. Brain Res 1359:14–21

    PubMed  CAS  Google Scholar 

  96. Nass D, Rosenwald S, Meiri E, Gilad S, Tabibian-Keissar H, Schlosberg A et al (2009) MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can be used to differentiate primary from metastatic brain tumors. Brain Pathol 19:375–383

    PubMed  CAS  Google Scholar 

  97. Fineberg SK, Kosik KS, Davidson BL (2009) MicroRNAs potentiate neural development. Neuron 64:303–309

    PubMed  CAS  Google Scholar 

  98. Fasano CA, Phoenix TN, Kokovay E, Lowry N, Elkabetz Y, Dimos JT et al (2009) Bmi-1 cooperates with Foxg1 to maintain neural stem cell self-renewal in the forebrain. Genes Dev 23:561–574

    PubMed  CAS  Google Scholar 

  99. Luan S, Sun L, Huang F (2010) MicroRNA-34a: a novel tumor suppressor in p53-mutant glioma cell line U251. Arch Med Res 41:67–74

    PubMed  CAS  Google Scholar 

  100. Guessous F, Zhang Y, Kofman A, Catania A, Li Y, Schiff D et al (2010) microRNA-34a is tumor suppressive in brain tumors and glioma stem cells. Cell Cycle 9

  101. Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E et al (2009) MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res 69:7569–7576

    PubMed  CAS  Google Scholar 

  102. Kefas B, Comeau L, Floyd DH, Seleverstov O, Godlewski J, Schmittgen T et al (2009) The neuronal microRNA miR-326 acts in a feedback loop with notch and has therapeutic potential against brain tumors. J Neurosci 29:15161–15168

    PubMed  CAS  Google Scholar 

  103. Malzkorn B, Wolter M, Liesenberg F, Grzendowski M, Stuhler K, Meyer HE et al (2009) Identification and functional characterization of microRNAs involved in the malignant progression of gliomas. Brain Pathol

  104. Laneve P, Di Marcotullio L, Gioia U, Fiori ME, Ferretti E, Gulino A et al (2007) The interplay between microRNAs and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells. Proc Natl Acad Sci U S A 104:7957–7962

    PubMed  CAS  Google Scholar 

  105. Ferretti E, De Smaele E, Po A, Di Marcotullio L, Tosi E, Espinola MS et al (2009) MicroRNA profiling in human medulloblastoma. Int J Cancer 124:568–577

    PubMed  CAS  Google Scholar 

  106. Sasayama T, Nishihara M, Kondoh T, Hosoda K, Kohmura E (2009) MicroRNA-10b is overexpressed in malignant glioma and associated with tumor invasive factors, uPAR and RhoC. Int J Cancer 125:1407–1413

    PubMed  CAS  Google Scholar 

  107. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E et al (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99:15524–15529

    PubMed  CAS  Google Scholar 

  108. Xia H, Qi Y, Ng SS, Chen X, Chen S, Fang M et al (2009) MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells. Biochem Biophys Res Commun 380:205–210

    PubMed  CAS  Google Scholar 

  109. Rao SA, Santosh V, Somasundaram K (2010) Genome-wide expression profiling identifies deregulated miRNAs in malignant astrocytoma. Mod Pathol 23:1404–1417

    PubMed  CAS  Google Scholar 

  110. Ferretti E, De Smaele E, Miele E, Laneve P, Po A, Pelloni M et al (2008) Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO J 27:2616–2627

    PubMed  CAS  Google Scholar 

  111. Pierson J, Hostager B, Fan R, Vibhakar R (2008) Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. J Neurooncol 90:1–7

    PubMed  CAS  Google Scholar 

  112. Song L, Huang Q, Chen K, Liu L, Lin C, Dai T et al (2010) miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-beta. Biochem Biophys Res Commun 402:135–140

    PubMed  CAS  Google Scholar 

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González-Gómez, P., Sánchez, P. & Mira, H. MicroRNAs as Regulators of Neural Stem Cell-Related Pathways in Glioblastoma Multiforme. Mol Neurobiol 44, 235–249 (2011). https://doi.org/10.1007/s12035-011-8196-y

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