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miRNA Expression and Functions in Glioma and Glioma Stem Cells

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MicroRNA Targeted Cancer Therapy

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Abstract

Glioblastoma (GBMs) are the most common and aggressive primary brain tumors. Current treatments include surgery, radiation therapy, and chemotherapy. Unfortunately, prognosis remains extremely poor and the median survival of 12–14 months in GBM has not changed significantly. GBMs contain a small subpopulation of glioma stem cells (GSCs) that are implicated in therapeutic resistance and tumor recurrence. Thus, the development of new therapeutic strategies to target these cells is of utmost significance. MicroRNAs (miRNAs) have been reported to play a major role in cancer development and progression and are now emerge as potential therapeutic targets in various tumors. This chapter reviews the expression of miRNAs in GBM and GSCs and their use as diagnostic and prognostic biomarkers and discusses the role of specific miRNAs in GSC functions and their potential use as therapeutic targets. Since the clinical use of miRNAs is hindered by lack of effective delivery mechanisms to tumor sites, a particular focus is placed on the possible modes of delivery of miRNA mimics or antagonists focusing on viral vectors, nanoparticles, exosomes and stem cells.

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References

  1. Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21:2683–2710

    PubMed  CAS  Google Scholar 

  2. Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, DePinho RA (2001) Malignant glioma: genetics and biology of a grave matter. Genes Dev 15:1311–1333

    PubMed  CAS  Google Scholar 

  3. James CD, Carlbom E, Dumanski JP, Hansen M, Nordenskjold M, Collins VP, Cavenee WK (1988) Clonal genomic alterations in glioma malignancy stages. Cancer Res 48:5546–5551

    PubMed  CAS  Google Scholar 

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

    PubMed Central  PubMed  Google Scholar 

  5. Cloughesy TF, Cavenee WK, Mischel PS (2014) Glioblastoma: from molecular pathology to targeted treatment. Annu Rev Pathol 9:1–25

    PubMed  CAS  Google Scholar 

  6. Maher EA, Brennan C, Wen PY, Durso L, Ligon KL, Richardson A, Khatry D, Feng B, Sinha R, Louis DN, Quackenbush J, Black PM, Chin L, DePinho RA (2006) Marked genomic differences characterize primary and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities. Cancer Res 66:11502–11513

    PubMed  CAS  Google Scholar 

  7. Reddy SP, Britto R, Vinnakota K, Aparna H, Sreepathi HK, Thota B, Kumari A, Shilpa BM, Vrinda M, Umesh S, Samuel C, Shetty M, Tandon A, Pandey P, Hegde S, Hegde AS, Balasubramaniam A, Chandramouli BA, Santosh V, Kondaiah P, Somasundaram K, Rao MR (2008) Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis. Clin Cancer Res 14:2978–2987

    PubMed  CAS  Google Scholar 

  8. Olar A, Aldape KD (2012) Biomarkers classification and therapeutic decision-making for malignant gliomas. Curr Treat Options Oncol 13:417–436

    PubMed  Google Scholar 

  9. Farias-Eisner G, Bank AM, Hwang BY, Appelboom G, Piazza MA, Bruce SS, Sander Connolly E (2012) Glioblastoma biomarkers from bench to bedside: advances and challenges. Br J Neurosurg 26:189–194

    PubMed  Google Scholar 

  10. Lawler S, Chiocca EA (2009) Emerging functions of microRNAs in glioblastoma. J Neurooncol 92:297–306

    PubMed  CAS  Google Scholar 

  11. Kim TM, Huang W, Park R, Park PJ, Johnson MD (2011) A developmental taxonomy of glioblastoma defined and maintained by MicroRNAs. Cancer Res 71:3387–3399

    PubMed Central  PubMed  CAS  Google Scholar 

  12. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K (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 

  13. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN, CGAR Network (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 Central  PubMed  CAS  Google Scholar 

  14. Masui K, Cloughesy TF, Mischel PS (2012) Review: molecular pathology in adult high-grade gliomas: from molecular diagnostics to target therapies. Neuropathol Appl Neurobiol 38:271–291

    PubMed  CAS  Google Scholar 

  15. Lin J, Teo S, Lam DH, Jeyaseelan K, Wang S (2012) MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme. Cell Death Dis 3:e398

    PubMed Central  PubMed  CAS  Google Scholar 

  16. Franco-Chuaire ML, Magda Carolina SC, Chuaire-Noack L (2013) Epithelial-mesenchymal transition (EMT): principles and clinical impact in cancer therapy. Invest Clin 54:186–205

    PubMed  Google Scholar 

  17. Tiwari N, Gheldof A, Tatari M, Christofori G (2012) EMT as the ultimate survival mechanism of cancer cells. Semin Cancer Biol 22:194–207

    PubMed  CAS  Google Scholar 

  18. Tso CL, Shintaku P, Chen J, Liu Q, Liu J, Chen Z, Yoshimoto K, Mischel PS, Cloughesy TF, Liau LM, Nelson SF (2006) Primary glioblastomas express mesenchymal stem-like properties. Mol Cancer Res 4:607–619

    PubMed  CAS  Google Scholar 

  19. Ricci-Vitiani L, Pallini R, Larocca LM, Lombardi DG, Signore M, Pierconti F, Petrucci G, Montano N, Maira G, De Maria R (2008) Mesenchymal differentiation of glioblastoma stem cells. Cell Death Differ 15:1491–1498

    PubMed  CAS  Google Scholar 

  20. Rieske P, Golanska E, Zakrzewska M, Piaskowski S, Hulas-Bigoszewska K, Wolańczyk M, Szybka M, Witusik-Perkowska M, Jaskolski DJ, Zakrzewski K, Biernat W, Krynska B, Liberski PP (2009) Arrested neural and advanced mesenchymal differentiation of glioblastoma cells-comparative study with neural progenitors. BMC Cancer 9:54

    PubMed Central  PubMed  Google Scholar 

  21. deCarvalho AC, Nelson K, Lemke N, Lehman NL, Arbab AS, Kalkanis S, Mikkelsen T (2010) Gliosarcoma stem cells undergo glial and mesenchymal differentiation in vivo. Stem Cells 28:181–190

    PubMed Central  PubMed  CAS  Google Scholar 

  22. Beier CP, Kumar P, Meyer K, Leukel P, Bruttel V, Aschenbrenner I, Riemenschneider MJ, Fragoulis A, Rümmele P, Lamszus K, Schulz JB, Weis J, Bogdahn U, Wischhusen J, Hau P, Spang R, Beier D (2012) The cancer stem cell subtype determines immune infiltration of glioblastoma. Stem Cells Dev 2:2753–2761

    Google Scholar 

  23. Bhat KP, Balasubramaniyan V, Vaillant B, Ezhilarasan R, Hummelink K, Hollingsworth F, Wani K, Heathcock L, James JD, Goodman LD, Conroy S, Long L, Lelic N, Wang S, Gumin J, Raj D, Kodama Y, Raghunathan A, Olar A, Joshi K, Pelloski CE, Heimberger A, Kim SH, Cahill DP, Rao G, Den Dunnen WF, Boddeke HW, Phillips HS, Nakano I, Lang FF, Colman H, Sulman EP, Aldape K (2013) Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma. Cancer Cell 24:331–346

    PubMed  CAS  Google Scholar 

  24. Carro MS, Lim WK, Alvarez MJ, Bollo RJ, Zhao X, Snyder EY, Sulman EP, Anne SL, Doetsch F, Colman H, Lasorella A, Aldape K, Califano A, Iavarone A (2010) The transcriptional network for mesenchymal transformation of brain tumours. Nature 463:318–325

    PubMed  CAS  Google Scholar 

  25. Bhat KP, Salazar KL, Balasubramaniyan V, Wani K, Heathcock L, Hollingsworth F, James JD, Gumin J, Diefes KL, Kim SH, Turski A, Azodi Y, Yang Y, Doucette T, Colman H, Sulman EP, Lang FF, Rao G, Copray S, Vaillant BD, Aldape KD (2011) The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma. Genes Dev 25:2594–2609

    PubMed Central  PubMed  CAS  Google Scholar 

  26. Yan J, Gumireddy K, Li A, Huang Q (2013) Regulation of mesenchymal phenotype by MicroRNAs in cancer. Curr Cancer Drug Targets 13:930–934

    PubMed  CAS  Google Scholar 

  27. Karsy M, Arslan E, Moy F (2012) Current progress on understanding MicroRNAs in glioblastoma multiforme. Genes Cancer 3:3–15

    PubMed Central  PubMed  Google Scholar 

  28. Møller HG, Rasmussen AP, Andersen HH, Johnsen KB, Henriksen M, Duroux M (2013) A systematic review of microRNA in glioblastoma multiforme: micro-modulators in the mesenchymal mode of migration and invasion. Mol Neurobiol 47:131–144

    PubMed Central  PubMed  Google Scholar 

  29. Magee JA, Piskounova E, Morrison SJ (2012) Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 21:283–296

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  31. Gupta PB, Chaffer CL, Weinberg RA (2009) Cancer stem cells: mirage or reality? Nat Med 15:1010–1012

    PubMed  CAS  Google Scholar 

  32. Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8:755–768

    PubMed  CAS  Google Scholar 

  33. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    PubMed  CAS  Google Scholar 

  34. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401

    PubMed  CAS  Google Scholar 

  35. Venere M, Fine HA, Dirks PB, Rich JN (2011) Cancer stem cells in gliomas: identifying and understanding the apex cell in cancer’s hierarchy. Glia 59:1148–1154

    PubMed Central  PubMed  Google Scholar 

  36. Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6:425–436

    PubMed  CAS  Google Scholar 

  37. Stiles CD, Rowitch DH (2008) Glioma stem cells: a midterm exam. Neuron 58:832–846

    PubMed  CAS  Google Scholar 

  38. Park DM, Rich JN (2009) Biology of glioma cancer stem cells. Mol Cells 28:7–12

    PubMed  CAS  Google Scholar 

  39. Swartling FJ, Bolin S, Phillips JJ, Persson AI (2013) Signals that regulate the oncogenic fate of neural stem cells and progenitors. Exp Neurol (in press)

    Google Scholar 

  40. Chen J, McKay RM, Parada LF (2012) Malignant glioma: lessons from genomics, mouse models, and stem cells. Cell 149:36–47

    PubMed Central  PubMed  CAS  Google Scholar 

  41. Sampetrean O, Saya H (2013) Characteristics of glioma stem cells. Brain Tumor Pathol 30(4):209–214

    PubMed  CAS  Google Scholar 

  42. Stopschinski BE, Beier CP, Beier D (2013) Glioblastoma cancer stem cells – from concept to clinical application. Cancer Lett 338:32–40

    PubMed  CAS  Google Scholar 

  43. Ahmed AU, Auffinger B, Lesniak MS (2013) Understanding glioma stem cells: rationale, clinical relevance and therapeutic strategies. Expert Rev Neurother 13:545–555

    PubMed  CAS  Google Scholar 

  44. Zeng Y (2006) Principles of micro-RNA production and maturation. Oncogene 25:6156–6162

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  46. Rana TM (2007) Illuminating the silence: understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol 8:23–36

    PubMed  CAS  Google Scholar 

  47. Mitra CK, Korla K (2014) Functional, structural, and sequence studies of MicroRNA. Methods Mol Biol 1107:189–206

    PubMed  Google Scholar 

  48. Alvarez-Garcia I, Miska EA (2005) MicroRNA functions in animal development and human disease. Development 132:4653–4662

    PubMed  CAS  Google Scholar 

  49. Iorio MV, Croce CM (2012) MicroRNA involvement in human cancer. Carcinogenesis 33:1126–1133

    PubMed Central  PubMed  CAS  Google Scholar 

  50. Sun X, Jiao X, Pestell TG, Fan C, Qin S, Mirabelli E, Ren H, Pestell RG (2014) MicroRNAs and cancer stem cells: the sword and the shield. Oncogene (in press)

    Google Scholar 

  51. Godlewski J, Newton HB, Chiocca EA, Lawler SE (2010) MicroRNAs and glioblastoma; the stem cell connection. Cell Death Differ 17:221–228

    PubMed  CAS  Google Scholar 

  52. Zhang Y, Dutta A, Abounader R (2012) The role of microRNAs in glioma initiation and progression. Front Biosci (Landmark Ed) 17:700–712

    CAS  Google Scholar 

  53. Suh SS, Yoo JY, Nuovo GJ, Jeon YJ, Kim S, Lee TJ, Kim T, Bakàcs A, Alder H, Kaur B, Aqeilan RI, Pichiorri F, Croce CM (2012) MicroRNAs/TP53 feedback circuitry in glioblastoma multiforme. Proc Natl Acad Sci U S A 109:5316–5321

    PubMed Central  PubMed  CAS  Google Scholar 

  54. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T (2007) Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39:673–677

    PubMed  CAS  Google Scholar 

  55. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101:2999–3004

    PubMed Central  PubMed  CAS  Google Scholar 

  56. Baer C, Claus R, Plass C (2013) Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res 73:473–477

    PubMed  CAS  Google Scholar 

  57. Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, Liu CG, Giannakakis A, Alexiou P, Hasegawa K, Johnstone CN, Megraw MS, Adams S, Lassus H, Huang J, Kaur S, Liang S, Sethupathy P, Leminen A, Simossis VA, Sandaltzopoulos R, Naomoto Y, Katsaros D, Gimotty PA, DeMichele A, Huang Q, Bützow R, Rustgi AK, Weber BL, Birrer MJ, Hatzigeorgiou AG, Croce CM, Coukos G (2008) Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci U S A 105:7004–7009

    PubMed Central  PubMed  CAS  Google Scholar 

  58. Kent OA, Mendell JT (2006) A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene 25:6188–6196

    PubMed  CAS  Google Scholar 

  59. Pencheva N, Tavazoie SF (2013) Control of metastatic progression by microRNA regulatory networks. Nat Cell Biol 15:546–554

    PubMed  CAS  Google Scholar 

  60. Di Leva G, Croce CM (2013) miRNA profiling of cancer. Curr Opin Genet Dev 23:3–11

    PubMed Central  PubMed  Google Scholar 

  61. Srivastava SK, Bhardwaj A, Leavesley SJ, Grizzle WE, Singh S, Singh AP (2013) MicroRNAs as potential clinical biomarkers: emerging approaches for their detection. Biotech Histochem 88:373–387

    PubMed  CAS  Google Scholar 

  62. Riddick G, Fine HA (2011) Integration and analysis of genome-scale data from gliomas. Nat Rev Neurol 7:439–450

    PubMed  CAS  Google Scholar 

  63. Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X (2010) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer 127:118–126

    PubMed  CAS  Google Scholar 

  64. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    PubMed  CAS  Google Scholar 

  65. Iorio MV, Croce CM (2012) MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 4:143–159

    PubMed Central  PubMed  CAS  Google Scholar 

  66. Hermansen SK, Kristensen BW (2013) MicroRNA biomarkers in glioblastoma. J Neurooncol 114:13–23

    PubMed  CAS  Google Scholar 

  67. Ma X, Yoshimoto K, Guan Y, Hata N, Mizoguchi M, Sagata N, Murata H, Kuga D, Amano T, Nakamizo A, Sasaki T (2012) Associations between microRNA expression and mesenchymal marker gene expression in glioblastoma. Neuro Oncol 14:1153–1162

    PubMed Central  PubMed  CAS  Google Scholar 

  68. Li Y, Xu J, Chen H, Bai J, Li S, Zhao Z, Shao T, Jiang T, Ren H, Kang C, Li X (2013) Comprehensive analysis of the functional microRNA-mRNA regulatory network identifies miRNA signatures associated with glioma malignant progression. Nucleic Acids Res 41:e203

    PubMed Central  PubMed  CAS  Google Scholar 

  69. Baraniskin A, Kuhnhenn J, Schlegel U, Maghnouj A, Zöllner H, Schmiegel W, Hahn S, Schroers R (2012) Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma. Neuro Oncol 14:29–33

    PubMed Central  PubMed  CAS  Google Scholar 

  70. Wang Y, Gao X, Wei F, Zhang X, Yu J, Zhao H, Sun Q, Yan F, Yan C, Li H, Ren X (2014) Diagnostic and prognostic value of circulating miR-21 for cancer: a systematic review and meta-analysis. Gene 533:389–397

    PubMed  CAS  Google Scholar 

  71. 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 Central  PubMed  CAS  Google Scholar 

  72. Wu Z, Sun L, Wang H, Yao J, Jiang C, Xu W, Yang Z (2012) MiR-328 expression is decreased in high-grade gliomas and is associated with worse survival in primary glioblastoma. PLoS One 7:e47270

    PubMed Central  PubMed  CAS  Google Scholar 

  73. Zhang W, Zhang J, Hoadley K, Kushwaha D, Ramakrishnan V, Li S, Kang C, You Y, Jiang C, Song SW, Jiang T, Chen CC (2012) miR-181d: a predictive glioblastoma biomarker that downregulates MGMT expression. Neuro Oncol 14:712–719

    PubMed Central  PubMed  CAS  Google Scholar 

  74. Lee HK, Bier A, Cazacu S, Finniss S, Xiang C, Twito H, Poisson LM, Mikkelsen T, Slavin S, Jacoby E, Yalon M, Toren A, Rempel SA, Brodie C (2013) MicroRNA-145 is downregulated in glial tumors and regulates glioma cell migration by targeting connective tissue growth factor. PLoS One 8:e54652

    PubMed Central  PubMed  CAS  Google Scholar 

  75. Bier A, Giladi N, Kronfeld N, Lee HK, Cazacu S, Finniss S, Xiang C, Poisson L, de Carvalho AC, Slavin S, Jacoby E, Yalon M, Toren A, Mikkelsen T, Brodie C (2013) MicroRNA-137 is downregulated in glioblastoma and inhibits the stemness of glioma stem cells by targeting RTVP-1. Oncotarget 4:665–676

    PubMed Central  PubMed  Google Scholar 

  76. Auffinger B, Thaci B, Ahmed A, Ulasov I, Lesniak MS (2013) MicroRNA targeting as a therapeutic strategy against glioma. Curr Mol Med 13:535–542

    PubMed  CAS  Google Scholar 

  77. Hummel R, Maurer J, Haier J (2011) MicroRNAs in brain tumors: a new diagnostic and therapeutic perspective? Mol Neurobiol 44:223–234

    PubMed  CAS  Google Scholar 

  78. Cheng CJ, Slack FJ (2012) The duality of oncomiR addiction in the maintenance and treatment of cancer. Cancer J 18:232–237

    PubMed Central  PubMed  Google Scholar 

  79. Chistiakov DA, Chekhonin VP (2012) Contribution of microRNAs to radio- and chemoresistance of brain tumors and their therapeutic potential. Eur J Pharmacol 684:8–18

    PubMed  CAS  Google Scholar 

  80. Besse A, Sana J, Fadrus P, Slaby O (2013) MicroRNAs involved in chemo- and radioresistance of high-grade gliomas. Tumour Biol 34:1969–1978

    PubMed  CAS  Google Scholar 

  81. Palumbo S, Miracco C, Pirtoli L, Comincini S (2014) Emerging roles of microRNA in modulating cell-death processes in malignant glioma. J Cell Physiol 229:277–286

    PubMed  CAS  Google Scholar 

  82. Chen L, Zhang W, Yan W, Han L, Zhang K, Shi Z, Zhang J, Wang Y, Li Y, Yu S, Pu P, Jiang C, Jiang T, Kang C (2012) The putative tumor suppressor miR-524-5p directly targets Jagged-1 and Hes-1 in glioma. Carcinogenesis 33:2276–2282

    PubMed  CAS  Google Scholar 

  83. Huse JT, Brennan C, Hambardzumyan D, Wee B, Pena J, Rouhanifard SH, Sohn-Lee C, le Sage C, Agami R, Tuschl T, Holland EC (2009) The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo. Genes Dev 23:1327–1337

    PubMed Central  PubMed  CAS  Google Scholar 

  84. Kefas B, Godlewski J, Comeau L, Li Y, Abounader R, Hawkinson M, Lee J, Fine H, Chiocca EA, Lawler S, Purow B (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 

  85. Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438:685–689

    PubMed  Google Scholar 

  86. Fabbri E, Brognara E, Borgatti M, Lampronti I, Finotti A, Bianchi N, Sforza S, Tedeschi T, Manicardi A, Marchelli R, Corradini R, Gambari R (2011) miRNA therapeutics: delivery and biological activity of peptide nucleic acids targeting miRNAs. Epigenomics 3:733–745

    PubMed  CAS  Google Scholar 

  87. Ørom UA, Kauppinen S, Lund AH (2006) LNA-modified oligonucleotides mediate specific inhibition of microRNA function. Gene 372:137–141

    PubMed  Google Scholar 

  88. Obad S, dos Santos CO, Petri A, Heidenblad M, Broom O, Ruse C, Fu C, Lindow M, Stenvang J, Straarup EM, Hansen HF, Koch T, Pappin D, Hannon GJ, Kauppinen S (2011) Silencing of microRNA families by seed-targeting tiny LNAs. Nat Genet 43:371–378

    PubMed Central  PubMed  CAS  Google Scholar 

  89. Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4:721–726

    PubMed  CAS  Google Scholar 

  90. Yang G, Yin B (2014) The advance of application for microRNAs in cancer gene therapy. Biomed Pharmacother 68:137–142

    PubMed  CAS  Google Scholar 

  91. Fabbri M (2013) MicroRNAs and cancer: towards a personalized medicine. Curr Mol Med 13:751–756

    PubMed  CAS  Google Scholar 

  92. 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 

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

    PubMed Central  PubMed  CAS  Google Scholar 

  94. 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 

  95. 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 

  96. Ueda R, Kohanbash G, Sasaki K, Fujita M, Zhu X, Kastenhuber ER, McDonald HA, Potter DM, Hamilton RL, Lotze MT, Khan SA, Sobol RW, Okada H (2009) Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proc Natl Acad Sci U S A 106:10746–10751

    PubMed Central  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  98. Wei J, Wang F, Kong LY, Xu S, Doucette T, Ferguson SD, Yang Y, McEnery K, Jethwa K, Gjyshi O, Qiao W, Levine NB, Lang FF, Rao G, Fuller GN, Calin GA, Heimberger AB (2013) miR-124 inhibits STAT3 signaling to enhance T cell-mediated immune clearance of glioma. Cancer Res 73:3913–3926

    PubMed  CAS  Google Scholar 

  99. Speranza MC, Frattini V, Pisati F, Kapetis D, Porrati P, Eoli M, Pellegatta S, Finocchiaro G (2012) NEDD9, a novel target of miR-145, increases the invasiveness of glioblastoma. Oncotarget 3:723–734

    PubMed Central  PubMed  Google Scholar 

  100. Rani SB, Rathod SS, Karthik S, Kaur N, Muzumdar D, Shiras AS (2013) MiR-145 functions as a tumor-suppressive RNA by targeting Sox9 and adducin 3 in human glioma cells. Neuro Oncol 15:1302–1316

    PubMed  CAS  Google Scholar 

  101. Lavon I, Zrihan D, Granit A, Einstein O, Fainstein N, Cohen MA, Zelikovitch B, Shoshan Y, Spektor S, Reubinoff BE, Felig Y, Gerlitz O, Ben-Hur T, Smith Y, Siegal T (2010) Gliomas display a microRNA expression profile reminiscent of neural precursor cells. Neuro Oncol 12:422–433

    PubMed Central  PubMed  CAS  Google Scholar 

  102. Lang MF, Yang S, Zhao C, Sun G, Murai K, Wu X, Wang J, Gao H, Brown CE, Liu X, Zhou J, Peng L, Rossi JJ, Shi Y (2012) Genome-wide profiling identified a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. PLoS One 7:e36248

    PubMed Central  PubMed  CAS  Google Scholar 

  103. Godlewski J, Nowicki MO, Bronisz A, Nuovo G, Palatini J, De Lay M, Van Brocklyn J, Ostrowski MC, Chiocca EA, Lawler SE (2010) MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol Cell 37:620–632

    PubMed Central  PubMed  CAS  Google Scholar 

  104. Fareh M, Turchi L, Virolle V, Debruyne D, Almairac F, de-la-Forest Divonne S, Paquis P, Preynat-Seauve O, Krause KH, Chneiweiss H, Virolle T (2012) The miR 302–367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network. Cell Death Differ 19:232–244

    PubMed Central  PubMed  CAS  Google Scholar 

  105. Katsushima K, Shinjo K, Natsume A, Ohka F, Fujii M, Osada H, Sekido Y, Kondo Y (2012) Contribution of microRNA-1275 to Claudin11 protein suppression via a polycomb-mediated silencing mechanism in human glioma stem-like cells. J Biol Chem 287:27396–27406

    PubMed Central  PubMed  CAS  Google Scholar 

  106. Schraivogel D, Weinmann L, Beier D, Tabatabai G, Eichner A, Zhu JY, Anton M, Sixt M, Weller M, Beier CP, Meister G (2011) CAMTA1 is a novel tumour suppressor regulated by miR-9/9* in glioblastoma stem cells. EMBO J 30:4309–4322

    PubMed Central  PubMed  CAS  Google Scholar 

  107. Jeon HM, Sohn YW, Oh SY, Kim SH, Beck S, Kim S, Kim H (2011) ID4 imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9*-mediated suppression of SOX2. Cancer Res 71:3410–3421

    PubMed  CAS  Google Scholar 

  108. Xia H, Cheung WK, Ng SS, Jiang X, Jiang S, Sze J, Leung GK, Lu G, Chan DT, Bian XW, Kung HF, Poon WS, Lin MC (2012) Loss of brain-enriched miR-124 microRNA enhances stem-like traits and invasiveness of glioma cells. J Biol Chem 287:9962–9971

    PubMed Central  PubMed  CAS  Google Scholar 

  109. Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, Vandenberg SR, Ginzinger DG, James CD, Costello JF, Bergers G, Weiss WA, Alvarez-Buylla A, Hodgson JG (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 Central  PubMed  Google Scholar 

  110. Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen TD, Lopes B, Schiff D, Purow B, Abounader R (2009) MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res 69:7569–7576

    PubMed Central  PubMed  CAS  Google Scholar 

  111. Guessous F, Zhang Y, Kofman A, Catania A, Li Y, Schiff D, Purow B, Abounader R (2010) MicroRNA-34a is tumor suppressive in brain tumors and glioma stem cells. Cell Cycle 9:1031–1036

    PubMed Central  PubMed  CAS  Google Scholar 

  112. Kefas B, Comeau L, Floyd DH, Seleverstov O, Godlewski J, Schmittgen T, Jiang J, diPierro CG, Li Y, Chiocca EA, Lee J, Fine H, Abounader R, Lawler S, Purow B (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 Central  PubMed  CAS  Google Scholar 

  113. Ernst A, Campos B, Meier J, Devens F, Liesenberg F, Wolter M, Reifenberger G, Herold-Mende C, Lichter P, Radlwimmer B (2010) De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures. Oncogene 29:3411–3422

    PubMed  CAS  Google Scholar 

  114. Godlewski J, Nowicki MO, Bronisz A, Williams S, Otsuki A, Nuovo G, Raychaudhury A, Newton HB, Chiocca EA, Lawler S (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 

  115. Lee HK, Finniss S, Cazacu S, Bucris E, Ziv-Av A, Xiang C, Bobbitt K, Rempel SA, Hasselbach L, Mikkelsen T, Slavin S, Brodie C (2013) Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal. Oncotarget 4:346–361

    PubMed Central  PubMed  Google Scholar 

  116. Zhao S, Liu H, Liu Y, Wu J, Wang C, Hou X, Chen X, Yang G, Zhao L, Che H, Bi Y, Wang H, Peng F, Ai J (2013) miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells. Cancer Lett 333:253–260

    PubMed  CAS  Google Scholar 

  117. Serwer LP, James CD (2012) Challenges in drug delivery to tumors of the central nervous system: an overview of pharmacological and surgical considerations. Adv Drug Deliv Rev 64:590–597

    PubMed  CAS  Google Scholar 

  118. Liu YP, Berkhout B (2011) miRNA cassettes in viral vectors: problems and solutions. Biochim Biophys Acta 1809:732–745

    PubMed  CAS  Google Scholar 

  119. Couto LB, High KA (2010) Viral vector-mediated RNA interference. Curr Opin Pharmacol 10:534–542

    PubMed  CAS  Google Scholar 

  120. Zhang Y, Wang Z, Gemeinhart RA (2013) Progress in microRNA delivery. J Control Release 172:962–974

    PubMed  CAS  Google Scholar 

  121. Muthiah M, Park IK, Cho CS (2013) Nanoparticle-mediated delivery of therapeutic genes: focus on miRNA therapeutics. Expert Opin Drug Deliv 10:1259–1273

    PubMed  CAS  Google Scholar 

  122. Shu Y, Pi F, Sharma A, Rajabi M, Haque F, Shu D, Leggas M, Evers BM, Guo P (2014) Stable RNA nanoparticles as potential new generation drugs for cancer therapy. Adv Drug Deliv Rev 66C:74–89

    Google Scholar 

  123. Lee Y, El Andaloussi S, Wood MJ (2012) Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet 21:R125–R134

    PubMed  CAS  Google Scholar 

  124. Record M, Carayon K, Poirot M, Silvente-Poirot S (2014) Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies. Biochim Biophys Acta 1841:108–120

    PubMed  CAS  Google Scholar 

  125. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659

    PubMed  CAS  Google Scholar 

  126. Azmi AS, Bao B, Sarkar FH (2013) Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev 32:623–642

    PubMed  CAS  Google Scholar 

  127. Rayner KJ, Hennessy EJ (2013) Extracellular communication via microRNA: lipid particles have a new message. J Lipid Res 54:1174–1181

    PubMed  CAS  Google Scholar 

  128. Katakowski M, Buller B, Zheng X, Lu Y, Rogers T, Osobamiro O, Shu W, Jiang F, Chopp M (2013) Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett 335:201–204

    PubMed  CAS  Google Scholar 

  129. Munoz JL, Bliss SA, Greco SJ, Ramkissoon SH, Ligon KL, Rameshwar P (2013) Delivery of functional anti-miR-9 by mesenchymal stem cell-derived exosomes to glioblastoma multiforme cells conferred chemosensitivity. Mol Ther Nucleic Acids 2:e126

    PubMed  Google Scholar 

  130. Binello E, Germano IM (2012) Stem cells as therapeutic vehicles for the treatment of high-grade gliomas. Neuro Oncol 14:256–265

    PubMed Central  PubMed  CAS  Google Scholar 

  131. Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J, Hentschel S, Vecil G, Dembinski J, Andreeff M, Lang FF (2005) Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 65:3307–3318

    PubMed  CAS  Google Scholar 

  132. Choi SA, Lee JY, Wang KC, Phi JH, Song SH, Song J, Kim SK (2012) Human adipose tissue-derived mesenchymal stem cells: characteristics and therapeutic potential as cellular vehicles for prodrug gene therapy against brainstem gliomas. Eur J Cancer 48:129–137

    PubMed  CAS  Google Scholar 

  133. Gondi CS, Veeravalli KK, Gorantla B, Dinh DH, Fassett D, Klopfenstein JD, Gujrati M, Rao JS (2010) Human umbilical cord blood stem cells show PDGF-D-dependent glioma cell tropism in vitro and in vivo. Neuro Oncol 12:453–465

    PubMed Central  PubMed  CAS  Google Scholar 

  134. Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F (2008) Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther 15:730–738

    PubMed  CAS  Google Scholar 

  135. Lee SJ, Kim SJ, Seo HH, Shin SP, Kim D, Park CS, Kim KT, Kim YH, Jeong JS, Kim IH (2012) Over-expression of miR-145 enhances the effectiveness of HSVtk gene therapy for malignant glioma. Cancer Lett 320:72–80

    PubMed  CAS  Google Scholar 

  136. Wang X, Han L, Zhang A, Wang G, Jia Z, Yang Y, Yue X, Pu P, Shen C, Kang C (2011) Adenovirus-mediated shRNAs for co-repression of miR-221 and miR-222 expression and function in glioblastoma cells. Oncol Rep 25:97–105

    PubMed  Google Scholar 

  137. Costa PM, Cardoso AL, Mendonça LS, Serani A, Custódia C, Conceição M, Simões S, Moreira JN, Pereira de Almeida L, Pedroso de Lima MC (2013) Tumor-targeted Chlorotoxin-coupled nanoparticles for nucleic acid delivery to glioblastoma cells: a promising system for glioblastoma treatment. Mol Ther Nucleic Acids 2:e100

    PubMed Central  PubMed  Google Scholar 

  138. Yang YP, Chien Y, Chiou GY, Cherng JY, Wang ML, Lo WL, Chang YL, Huang PI, Chen YW, Shih YH, Chen MT, Chiou SH (2012) Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI. Biomaterials 33:1462–1476

    PubMed  CAS  Google Scholar 

  139. Wang W, Dai LX, Zhang S, Yang Y, Yan N, Fan P, Dai L, Tian HW, Cheng L, Zhang XM, Li C, Zhang JF, Xu F, Shi G, Chen XL, Du T, Li YM, Wei YQ, Deng HX (2013) Regulation of epidermal growth factor receptor signaling by plasmid-based microRNA-7 inhibits human malignant gliomas growth and metastasis in vivo. Neoplasma 60:274–283

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA

    Chaya Brodie & Hae Kyung Lee

  2. Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel

    Chaya Brodie & Efrat Buchris

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  1. Chaya Brodie
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  2. Efrat Buchris
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Correspondence to Chaya Brodie .

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  1. Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA

    Fazlul H. Sarkar

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Brodie, C., Buchris, E., Lee, H.K. (2014). miRNA Expression and Functions in Glioma and Glioma Stem Cells. In: Sarkar, F. (eds) MicroRNA Targeted Cancer Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-05134-5_2

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