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Glioblastoma is a brain tumor that develops due to both genetic and epigenetic risk factors. Crosstalk between the genetic and the epigenetic offers new possibilities for therapy. Abnormal methylation of methylguanine-DNA methyltransferase (MGMT) promoter region and isocitrate dehydrogenase 1 (IDH1) mutations are prognostic and therapeutic response markers in glioblastoma. Mutations in genes such as epidermal growth factor receptor, TP53, and P16 have been reported in glioblastoma; therefore, they might associate with survival and worth to be used in estimating survival risks. MKI67 expression associates with posttreatment such as adjuvant radiotherapy results evaluation. On the other hand, monosomies, such as deletions of chromosome 10, especially q23 and q25–26, are good markers for estimating the progression and aggressiveness of glioblastoma. The profile of MGMT methylation is modified in glioblastoma and hence can be a good target for epigenetic drugs. Other useful strategies in the treatment of gliomas include several micro-RNAs (MiRs) which are alerted in glioblastoma and which affect the regulation of mRNAs are associated with gene expression profiles of the disease. Epigenetic drugs, such as azacitidine and decitabine, which belong to the DNA methyltransferases (DNMT) inhibitor 5-aza-2'deoxycytidine (5-aza-dC), can suppress DNMT1 and stimulate tumor suppressor genes expression. MGMT methylation status and IDH mutational status are two valuable prognosis and therapeutic response markers in glioblastoma. Regulation of glioblastoma through epigenetic drugs, such as not only inhibitors of EZH2, histone deacetylase, and DNMT, but also MiRs, are promising approaches in glioblastoma treatment. Improves in understanding cancer genetic and epigenetic disruptions is the key point in solving the puzzle of glioblastoma treatment.
Introduction
Glioblastoma is one of the most common brain tumors [1],[2] with poor prognosis and limited chemotherapy efficiency as a result of the blood–brain barrier.[3] To improve the prognosis of glioblastoma, the minocycline, telmisartan, and zoledronic acid (MTZ) regimen were recommended, which includes MTZ.[4] Heterogeneity of glioblastoma investigates the variability of genetic and epigenetic of this tumor, changes in methylation pattern. Various mutations in different genes are responsible for glioblastoma.[1] Glioblastoma invades other organs through blood mostly and lymphatic pathways; however, this tumor has low potential of metastasis to out of central nerve system as a result of blood–brain barrier and absence of lymphatic vessels.[5] Mutations in genes such as epidermal growth factor receptor (EGFR), TP53, and P16 have been reported in glioblastoma, therefore, they might associate with survival, and they are worth being used in estimating survival risks.[6] A study on six metastatic glioblastomas investigated CDKN2A/P16 deletion; loss of alleles on chromosomes 1p, 10q and 19q, TP53 mutation, and EGFR amplification and interestingly metastasis occur mostly in young patients with TP53 mutation.[7] Recent studies demonstrated that the metastasis process can be affected by various molecules such as chemokines, pro-angiogenic factors, growth factors, extracellular matrix-remodeling proteins, and several micro-RNA (MiRs).[8] A study on IDH1 gene mutation in glioblastoma, with oligodendroglia appearance and1p19q deletion, showed a better response to chemotherapy in comparison to other mutations.[9] The most invasive mutation in astrocytic gliomas, a subtype of glioblastomas, is 9p21 deletion which can activate MYC signaling pathway.[10] At the molecular level, glioblastoma is characterized by different genetic and epigenetic changes that affect different oncogenes and tumor suppressor genes. However, few of these changes are known as prognostic and treatment response markers such as abnormal methylation of methylguanine-DNA methyltransferase (MGMT) promoter region and isocitrate dehydrogenase 1 (IDH1) mutations.[11] Genetic studies can assist in finding a therapeutic target, however; our knowledge is not enough yet.[12] Recent studies suggests that the origin of glioblastoma in the brain can be helpful in choosing the therapeutic method and estimating patients response.[13] Epigenetic modifications of tumor cells have been investigated in glioblastoma whereas epigenetic drugs are considered as good targets for glioblastoma therapeutic studies.[14] Recent therapeutic approaches, such as DNMT and histone deacetylase (HDAC) inhibitors, which overturn epigenetic effects, are intensively considered in neoplastic disorders and malignancies.[15] In this review, we discuss the genetics and epigenetics of glioblastoma and the effect of mutations on its features. We also discuss various treatment strategies such as epigenetic drugs, MiRs, and gene editing. The challenge is to classify glioblastomas according to genetic and epigenetic defects and to manage the treatment strategies according to tumor's genetic and epigenetic origins.
Glioblastoma Genetic and Possible Classification
Genome-wide profiling studies have investigated genomic heterogeneity among glioblastoma tumors, and different molecular signatures defined subclasses that can be useful in stratification of treatment.[16] However, mutation occurrence in glioblastoma is lower than other solid tumors.[17] On the other hand, loss of heterozygosity (LOH) among markers of the long arm of chromosome 10 (10q), which contains cancer genes such as PTEN, FGFR2, and MKI67, is detectable in up to 80% of glioblastoma cases.[11] In fact, monosomies such as deletions of chromosome 10, especially q23 and q25–26, are good markers for estimating the progression and aggressiveness of glioblastoma.[18] In astrocytomas and oligodendroglial tumors, which are subtypes of glioblastoma tumor, IDH mutations usually happen earlier than 1p deletion (del),9q del and tumor protein p53 (TP53) mutations.[19] Amplification of CDK and MDM2 oncogenes in glioblastoma disrupts P53 and RB pathways, and their mutations are associated with tumor progression.[17] Indeed, TP53, PTEN, and EGFR genes are the most frequently mutated genes in glioblastoma [Table 1].[20]{Table 1}
Epigenetics in Glioblastoma
Epigenetic risks such as allergies, atopic diseases, and systemic infections seem to be important in triggering glioblastoma, however; neither cigarette smoking nor alcohol consumption have been reported as risk factors.[46],[47] Sturm et al. dentified six epigenetic glioblastoma subgroups displaying characteristic global DNA methylation patterns harboring distinct hotspot mutations, DNA copy-number alterations, and transcriptomic patterns.[1] The most common epigenetic change in glioblastoma is the LOH of chromosome 10q.[44] Several cancer mutations cause changes in DNA methylation profile, histone modifications, and nucleosome positioning which disrupt vital signaling pathways.[48] Studies showed that several epigenetic changes such as methylation of LINE-1 to be associated with poor prognosis in primary glioblastoma patients.[49] Changes in promoter DNA methylation pattern are important in glioblastoma, especially if the methylation occurs in a promoter involved with crucial biologic pathways.[50] Abnormal methylation of the MGMT promoter region and mutations in IDH1 are two valuable prognosis and therapeutic response markers in glioblastoma.[51],[52] For instance, epigenetic changes such as changing MGMT methylation profile might result in a decrease in MSH2, MSH6, and PMS2 proteins in glioblastoma.[53] In fact, hypermethylation of several tumor suppressors, DNA repair genes, and cell-cycle regulators is associated with increased mutation rate and poor outcome in glioblastoma.[54] In addition, several studies showed that MGMT promoter methylation status can be a predictor of temozolomide response in glioblastoma.[55] Moreover, CHK2 that inhibits cell-cycle progression through decreasing cyclin-dependent kinases (CDK) activity has been found to be hypermethylated in gliomas.[56]
Developing Therapeutic Approaches According to Genetic and Epigenetic Changes
Mesenchymal stem cells (MSCs) have inhibitory effects on growth, invasion, and metastasis of solid tumors. Therefore, they can be considered as a therapeutic approach in tumor treatment although their exact role in tumor progression is still unknown.[57] Since glioblastoma tumors do not respond efficiently to chemotherapy, radiation, and they are not surgically curable, novel treatment methods are needed.[58] MiRs affect gene expression and are candidates for glioblastoma therapy. For instance, MiR-873 downregulate IGF2BP1 expression affecting negatively the carcinogenesis and metastasis of glioblastoma.[59] On the other hand, MiR610 decrease the proliferation and cell growth of glioblastoma through inhibiting CCND2 and AKT3 expression at the transcriptional and translational levels.[60] Long noncoding RNAs (lncRNAs) such as ASLNC22381 and ASLNC20819, which target IGF-1, play important roles in glioblastoma development and progression. Therefore, targeting lncRNAs might be an effective therapeutic approach.[61] Epigenetic modifications are altered in tumor cells, in comparison to normal tissues, which can be reverted by inhibitors interfering in epigenetic enzymatic activities. For example, 5-aza-2'-deoxycytidine (5-AZA-CdR) is an epigenetic drug which increases apoptosis in glioblastoma cells through caspase-8 pathway.[62]
Epigenetic drugs
Epigenetic drugs are undergoing clinical trials and some of them have been already approved for cancer treatment by the Food and Drug Administration and the European Medicines Agency.[63] Targeting epigenetic regulators such as EZH2 and BMI1proved to be effective in vitro and in vivo.[64] EZH2 interact with several lncRNAs, therefore, EZH2 inhibitors are used to potentially control glioblastoma progression.[61] Drugs which suppress DNMT1 hypomethylated the DNA across cell divisions and can stimulate tumor suppressor genes to be expressed. For instance, azacitidine and decitabine belong to the DNMT inhibitor 5-aza-2'deoxycytidine (5-aza-dC) which is a category of epigenetic drugs that have been approved by the FDA for the treatment of myelodysplastic syndromes, acute myeloid leukemia, and medulloblastoma.[55],[65] Combination treatment of epigenetic drugs such as HDACi and DNMT represent a new hope in glioblastoma treatment.[65]
Micro-RNAs
Micro-RNAs (MiRs) are types of noncoding RNAs that control gene expression at the posttranscriptional level.[66] MiRs play important regulatory roles in biological processes such as apoptosis, migration, and invasion.[67] Recent studies have investigated several MiRs that are alerted in glioblastoma and which affected the regulation of mRNAs associated with gene expression profiles.[68] A summary of several studies based on MiRs therapeutic potential as an epigenetic drug in glioblastoma is presented in [Table 2].{Table 2}
Genome editing technologies
Discovery of the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system, offered a path to genome engineering. CRISPR/Cas was first generated and applied in 2013; however, limitations such as vector delivering systems into cells are still the challenging point of this technology.[87] CRISPR/Cas-based genome editing technologies are supposed to increase our ability to engineer genetic changes in glioblastoma-derived neural stem cells.[88] Zinc finger-mediated gene editing for the treatment of glioblastoma has been taken to the clinic.[89] Hematopoietic stem cell transplantation and immunotherapy are suggested therapeutic approaches because they can induce tumor-specific T cells production to fight malignant gliomas.[90]
Conclusion and Future Perspectives
Glioblastoma is a brain tumor with high frequency of mutations and poor prognosis. Glioblastoma involves various genetic and epigenetic changes that render diagnosis and treatment very difficult. Various mutations in EGFR, TP53, and P16 have been reported in these tumors. Important genetic markers implicated in estimating prognosis include 1p19q deletion, MGMT methylation, and IDH mutational status. Hypermethylation of several tumor suppressors, DNA repair genes, and cell-cycle regulators is associated with increased mutation rate and poor outcome in glioblastoma. Since most of the genetic changes lead to epigenetic modifications, we hypothesize that glioblastoma develops as a result of epigenetic defects and that we could overcome glioblastoma by controlling the epigenetic changes. Hence, genetic and epigenetic changes can be benefit approaches in detecting the prognosis and treatment responses in glioblastoma. Regulation of glioblastoma through epigenetic drug such as not only inhibitors of EZH2, HDAC, and DNMT, but also MiRs, can be promising approaches in glioblastoma treatment because recent studies in these fields developed based on animal studies. Understanding cancer genetic and epigenetic disruptions are crucial for solving the puzzle of glioblastoma treatment. We recommend several studies based on combination regimens involving epigenetics and immunotherapy might be useful in increasing the hope of the treatment of glioblastoma.
Acknowledgment
We wish to thank all our colleagues in Golestan Hospital clinical research development unit, Ahvaz Jundishapur University of Medical Sciences. A special thanks to Professor Najmaldin Saki Hematology Phd in Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran who helped us in enriching this review.
Financial support and sponsorship
Nil.
Conflicts of interest
This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.
Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, et al. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 2012;22:425-37.
Sturm D, Bender S, Jones DT, Lichter P, Grill J, Becher O, et al. Paediatric and adult glioblastoma: Multiform (epi) genomic culprits emerge. Nat Rev Cancer 2014;14:92-107.
Lee DH, Ryu HW, Won HR, Kwon SH. Advances in epigenetic glioblastoma therapy. Oncotarget 2017;8:18577-89.
Salacz ME, Kast RE, Saki N, Brüning A, Karpel-Massler G, Halatsch ME, et al. Toward a noncytotoxic glioblastoma therapy: Blocking MCP-1 with the MTZ regimen. Onco Targets Ther 2016;9:2535-45.
Frank S, Kuhn SA, Brodhun M, Mueller U, Romeike B, Kosmehl H, et al. Metastatic glioblastoma cells use common pathways via blood and lymphatic vessels. Neurol Neurochir Pol 2009;43:183-90.
Rich JN, Hans C, Jones B, Iversen ES, McLendon RE, Rasheed BK, et al. Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res 2005;65:4051-8.
Park CC, Hartmann C, Folkerth R, Loeffler JS, Wen PY, Fine HA, et al. Systemic metastasis in glioblastoma may represent the emergence of neoplastic subclones. J Neuropathol Exp Neurol 2000;59:1044-50.
Ma L, Weinberg RA. Micromanagers of malignancy: Role of microRNAs in regulating metastasis. Trends Genet 2008;24:448-56.
Fernandez-Vega I, Quirk J, Norwood FL, Sibtain NA, Laxton R, Bodi I, et al. Gliomatosis cerebri type 1 with extensive involvement of the spinal cord and BRAF V600E mutation. Pathol Oncol Res 2014;20:215-20.
Nagane M, Huang HJ, Cavenee WK. Advances in the molecular genetics of gliomas. Curr Opin Oncol 1997;9:215-22.
Alekseeva EA, Kuznetsova EB, Tanas AS, Prozorenko EV, Zaytsev AM, Kurzhupov MI, et al. Loss of heterozygosity and uniparental disomy of chromosome region 10q23.3-26.3 in glioblastoma. Genes Chromosomes Cancer 2018;57:42-7.
Scrideli CA, Carlotti CG Jr., Okamoto OK, Andrade VS, Cortez MA, Motta FJ, et al. Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: Identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR. J Neurooncol 2008;88:281-91.
Nomura M, Mukasa A, Nagae G, Yamamoto S, Tatsuno K, Ueda H, et al. Distinct molecular profile of diffuse cerebellar gliomas. Acta Neuropathol 2017;134:941-56.
Sigalotti L, Fratta E, Coral S, Maio M. Epigenetic drugs as immunomodulators for combination therapies in solid tumors. Pharmacol Ther 2014;142:339-50.
Hatzimichael E, Crook T. Cancer epigenetics: New therapies and new challenges. J Drug Deliv 2013;2013:529312.
McLendon R, Friedman A, Bigner D, Van Meir EG, Brat DJ, Mastrogianakis GM, et al. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008;455:1061-8.
Bleeker FE, Molenaar RJ, Leenstra S. Recent advances in the molecular understanding of glioblastoma. J Neurooncol 2012;108:11-27.
Brat DJ, Cagle PT, Dillon DA, Hattab EM, McLendon RE, Miller MA, et al. Template for reporting results of biomarker testing of specimens from patients with tumors of the central nervous system. Arch Pathol Lab Med 2015;139:1087-93.
Bourne TD, Schiff D. Update on molecular findings, management and outcome in low-grade gliomas. Nat Rev Neurol 2010;6:695-701.
Zinn PO, Singh SK, Kotrotsou A, Abrol S, Thomas G, Mosley J, et al. Distinct radiomic phenotypes define glioblastoma TP53-PTEN-EGFR mutational landscape. Neurosurgery 2017;64:203-10.
Yoshimoto M, Cunha IW, Coudry RA, Fonseca FP, Torres CH, Soares FA, et al. FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome. Br J Cancer 2007;97:678-85.
Nakahara Y, Shiraishi T, Okamoto H, Mineta T, Oishi T, Sasaki K, et al. Detrended fluctuation analysis of genome-wide copy number profiles of glioblastomas using array-based comparative genomic hybridization. Neuro Oncol 2004;6:281-9.
Ader I, Delmas C, Skuli N, Bonnet J, Schaeffer P, Bono F, et al. Preclinical evidence that SSR128129E – A novel small-molecule multi-fibroblast growth factor receptor blocker – Radiosensitises human glioblastoma. Eur J Cancer 2014;50:2351-9.
Ntzeros K, Stanier P, Mazis D, Kritikos N, Rozis M, Anesidis E, et al. MKI67 (Marker of proliferation Ki-67); 2015.
Simon M, Hosen I, Gousias K, Rachakonda S, Heidenreich B, Gessi M, et al. TERT promoter mutations: A novel independent prognostic factor in primary glioblastomas. Neuro Oncol 2015;17:45-52.
Toedt G, Barbus S, Wolter M, Felsberg J, Tews B, Blond F, et al. Molecular signatures classify astrocytic gliomas by IDH1 mutation status. Int J Cancer 2011;128:1095-103.
Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law M, et al. At(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 2006;66:9852-61.
Hoang-Xuan K, Capelle L, Kujas M, Taillibert S, Duffau H, Lejeune J, et al. Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 2004;22:3133-8.
Dahiya S, Emnett RJ, Haydon DH, Leonard JR, Phillips JJ, Perry A, et al. BRAF-V600E mutation in pediatric and adult glioblastoma. Neuro Oncol 2014;16:318-9.
Riemenschneider MJ, Büschges R, Wolter M, Reifenberger J, Boström J, Kraus JA, et al. Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification. Cancer Res 1999;59:6091-6.
Rao SK, Edwards J, Joshi AD, Siu IM, Riggins GJ. A survey of glioblastoma genomic amplifications and deletions. J Neurooncol 2010;96:169-79.
Turner KM, Sun Y, Ji P, Granberg KJ, Bernard B, Hu L, et al. Genomically amplified akt3 activates DNA repair pathway and promotes glioma progression. Proc Natl Acad Sci U S A 2015;112:3421-6.
Fischer U, Leidinger P, Keller A, Folarin A, Ketter R, Graf N, et al. Amplicons on chromosome 12q13-21 in glioblastoma recurrences. Int J Cancer 2010;126:2594-602.
Frederick L, Wang XY, Eley G, James CD. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 2000;60:1383-7.
Knobbe CB, Reifenberger J, Reifenberger G. Mutation analysis of the ras pathway genes NRAS, HRAS, KRAS and BRAF in glioblastomas. Acta Neuropathol 2004;108:467-70.
Crespo I, Vital AL, Nieto AB, Rebelo O, Tão H, Lopes MC, et al. Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays. J Mol Diagn 2011;13:634-47.
Szerlip NJ, Pedraza A, Chakravarty D, Azim M, McGuire J, Fang Y, et al. Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. Proc Natl Acad Sci U S A 2012;109:3041-6.
Nakamura M, Yonekawa Y, Kleihues P, Ohgaki H. Promoter hypermethylation of the RB1 gene in glioblastomas. Lab Invest 2001;81:77-82.
Zhu Y, Harada T, Liu L, Lush ME, Guignard F, Harada C, et al. Inactivation of NF1 in CNS causes increased glial progenitor proliferation and optic glioma formation. Development 2005;132:5577-88.
Gallia GL, Rand V, Siu IM, Eberhart CG, James CD, Marie SK, et al. PIK3CA gene mutations in pediatric and adult glioblastoma multiforme. Mol Cancer Res 2006;4:709-14.
Weber GL, Parat MO, Binder ZA, Gallia GL, Riggins GJ. Abrogation of PIK3CA or PIK3R1 reduces proliferation, migration, and invasion in glioblastoma multiforme cells. Oncotarget 2011;2:833-49.
Quayle SN, Lee JY, Cheung LW, Ding L, Wiedemeyer R, Dewan RW, et al. Somatic mutations of PIK3R1 promote gliomagenesis. PLoS One 2012;7:e49466.
Kesari S, Schiff D, Drappatz J, LaFrankie D, Doherty L, Macklin EA, et al. Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res 2009;15:330-7.
Alekseeva E, Tanas A, Prozorenko E, Zaytsev A, Kirsanova O, Strelnikov V, et al. Molecular pathology of the 10q23.3-26.3 chromosome region in glioblastoma. Ann Oncol 2016;27 Suppl 6:131P.
López G, Oberheim Bush NA, Berger MS, Perry A, Solomon DA. Diffuse non-midline glioma with H3F3A K27M mutation: A prognostic and treatment dilemma. Acta Neuropathol Commun 2017;5:38.
Ohgaki H, Kleihues P. Epidemiology and etiology of gliomas. Acta Neuropathol 2005;109:93-108.
Goodenberger ML, Jenkins RB. Genetics of adult glioma. Cancer Genet 2012;205:613-21.
You JS, Jones PA. Cancer genetics and epigenetics: Two sides of the same coin? Cancer Cell 2012;22:9-20.
Ohka F, Natsume A, Motomura K, Kishida Y, Kondo Y, Abe T, et al. The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma. PLoS One 2011;6:e23332.
Etcheverry A, Aubry M, de Tayrac M, Vauleon E, Boniface R, Guenot F, et al. DNA methylation in glioblastoma: Impact on gene expression and clinical outcome. BMC Genomics 2010;11:701.
Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17:98-110.
Huttner A. Overview of primary brain tumors: Pathologic classification, epidemiology, molecular biology, and prognostic markers. Hematol Oncol Clin North Am 2012;26:715-32.
Felsberg J, Thon N, Eigenbrod S, Hentschel B, Sabel MC, Westphal M, et al. Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas. Int J Cancer 2011;129:659-70.
Carén H, Pollard SM, Beck S. The good, the bad and the ugly: Epigenetic mechanisms in glioblastoma. Mol Aspects Med 2013;34:849-62.
Kelly AD, Issa JJ. The promise of epigenetic therapy: Reprogramming the cancer epigenome. Curr Opin Genet Dev 2017;42:68-77.
Llinàs-Arias P, Esteller M. Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: An update. Open Biol 2017;7. pii: 170152.
Norozi F, Ahmadzadeh A, Shahrabi S, Vosoughi T, Saki N. Mesenchymal stem cells as a double-edged sword in suppression or progression of solid tumor cells. Tumour Biol 2016;37:11679-89.
Cloughesy TF, Cavenee WK, Mischel PS. Glioblastoma: From molecular pathology to targeted treatment. Annu Rev Pathol 2014;9:1-25.
Wang RJ, Li JW, Bao BH, Wu HC, Du ZH, Su JL, et al. MicroRNA-873 (miRNA-873) inhibits glioblastoma tumorigenesis and metastasis by suppressing the expression of IGF2BP1. J Biol Chem 2015;290:8938-48.
Mo X, Cao Q, Liang H, Liu J, Li H, Liu F, et al. MicroRNA-610 suppresses the proliferation of human glioblastoma cells by repressing CCND2 and AKT3. Mol Med Rep 2016;13:1961-6.
Clarke J, Penas C, Pastori C, Komotar RJ, Bregy A, Shah AH, et al. Epigenetic pathways and glioblastoma treatment. Epigenetics 2013;8:785-95.
Sigalotti L, Fratta E, Coral S, Cortini E, Covre A, Nicolay HJ, et al. Epigenetic drugs as pleiotropic agents in cancer treatment: Biomolecular aspects and clinical applications. J Cell Physiol 2007;212:330-44.
Nebbioso A, Carafa V, Benedetti R, Altucci L. Trials with 'epigenetic' drugs: An update. Mol Oncol 2012;6:657-82.
Jin X, Kim LJ, Wu Q, Wallace LC, Prager BC, Sanvoranart T, et al. Targeting glioma stem cells through combined BMI1 and EZH2 inhibition. Nat Med 2017;23:1352-61.
Yuan J, Llamas Luceño N, Sander B, Golas MM. Synergistic anti-cancer effects of epigenetic drugs on medulloblastoma cells. Cell Oncol (Dordr) 2017;40:263-79.
Winter J, Diederichs S. MicroRNA biogenesis and cancer. Methods Mol Biol 2011;676:3-22.
Ebert MS, Sharp PA. Roles for microRNAs in conferring robustness to biological processes. Cell 2012;149:515-24.
Zhou X, Ren Y, Moore L, Mei M, You Y, Xu P, et al. Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. Lab Invest 2010;90:144-55.
Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, et al. MiR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med 2008;6:14.
Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, Niers JM, et al. MiR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. Oncotarget 2010;1:710-20.
Zhang CZ, Zhang JX, Zhang AL, Shi ZD, Han L, Jia ZF, et al. MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma. Mol Cancer 2010;9:229.
Gal H, Pandi G, Kanner AA, Ram Z, Lithwick-Yanai G, Amariglio N, et al. MIR-451 and imatinib mesylate inhibit tumor growth of glioblastoma stem cells. Biochem Biophys Res Commun 2008;376:86-90.
Ernst A, Campos B, Meier J, Devens F, Liesenberg F, Wolter M, et al. De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures. Oncogene 2010;29:3411-22.
Schraivogel D, Weinmann L, Beier D, Tabatabai G, Eichner A, Zhu JY, et al. CAMTA1 is a novel tumour suppressor regulated by miR-9/9* in glioblastoma stem cells. EMBO J 2011;30:4309-22.
Cortez MA, Nicoloso MS, Shimizu M, Rossi S, Gopisetty G, Molina JR, et al. MiR-29b and miR-125a regulate podoplanin and suppress invasion in glioblastoma. Genes Chromosomes Cancer 2010;49:981-90.
Zhang W, Zhang J, Hoadley K, Kushwaha D, Ramakrishnan V, Li S, et al. MiR-181d: A predictive glioblastoma biomarker that downregulates MGMT expression. Neuro Oncol 2012;14:712-9.
Kouri FM, Hurley LA, Daniel WL, Day ES, Hua Y, Hao L, et al. MiR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma. Genes Dev 2015;29:732-45.
Chakrabarti M, Banik NL, Ray SK. Photofrin based photodynamic therapy and miR-99a transfection inhibited FGFR3 and PI3K/Akt signaling mechanisms to control growth of human glioblastoma in vitro and in vivo. PLoS One 2013;8:e55652.
Wei J, Wang F, Kong LY, Xu S, Doucette T, Ferguson SD, et al. MiR-124 inhibits STAT3 signaling to enhance T cell-mediated immune clearance of glioma. Cancer Res 2013;73:3913-26.
Zheng X, Chopp M, Lu Y, Buller B, Jiang F. MiR-15b and miR-152 reduce glioma cell invasion and angiogenesis via NRP-2 and MMP-3. Cancer Lett 2013;329:146-54.
Mathew LK, Skuli N, Mucaj V, Lee SS, Zinn PO, Sathyan P, et al. MiR-218 opposes a critical RTK-HIF pathway in mesenchymal glioblastoma. Proc Natl Acad Sci U S A 2014;111:291-6.
Jin Z, Xu S, Yu H, Yang B, Zhao H, Zhao G, et al. MiR-125b inhibits connexin43 and promotes glioma growth. Cell Mol Neurobiol 2013;33:1143-8.
Liu Z, Jiang Z, Huang J, Huang S, Li Y, Yu S, et al. MiR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and raf/MEK/ERK pathways. Int J Oncol 2014;44:1571-80.
Fowler A, Thomson D, Giles K, Maleki S, Mreich E, Wheeler H, et al. MiR-124a is frequently down-regulated in glioblastoma and is involved in migration and invasion. Eur J Cancer 2011;47:953-63.
Yin D, Ogawa S, Kawamata N, Leiter A, Ham M, Li D, et al. MiR-34a functions as a tumor suppressor modulating EGFR in glioblastoma multiforme. Oncogene 2013;32:1155-63.
Wang L, Shi M, Hou S, Ding B, Liu L, Ji X, et al. MiR-483-5p suppresses the proliferation of glioma cells via directly targeting ERK1. FEBS Lett 2012;586:1312-7.
Baek K, Tu C, Zoldan J, Suggs LJ. Gene transfection for stem cell therapy. Curr Stem Cell Rep 2016;2:52-61.
O'Duibhir E, Carragher NO, Pollard SM. Accelerating glioblastoma drug discovery: Convergence of patient-derived models, genome editing and phenotypic screening. Mol Cell Neurosci 2017;80:198-207.
Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. Genome editing with engineered zinc finger nucleases. Nat Rev Genet 2010;11:636-46.
Adair JE, Kubek SP, Kiem HP. Hematopoietic stem cell approaches to cancer. Hematol Oncol Clin North Am 2017;31:897-912.
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