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Critical role of HOX transcript antisense intergenic RNA (HOTAIR) in gliomas

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Abstract

Despite extensive research, gliomas are associated with high morbidity and mortality, mainly attributed to the rapid growth rate, excessive invasiveness, and molecular heterogeneity, as well as regenerative potential of cancer stem cells. Therefore, elucidation of the underlying molecular mechanisms and the identification of potential molecular diagnostic and prognostic biomarkers are of paramount importance. HOX transcript antisense intergenic RNA (HOTAIR) is a well-studied long noncoding RNA, playing an emerging role in tumorigenesis of several human cancers. A growing amount of preclinical and clinical evidence highlights the pro-oncogenic role of HOTAIR in gliomas, mainly attributed to the enhancement of proliferation and migration, as well as inhibition of apoptosis. In vitro and in vivo studies demonstrate that HOTAIR modulates the activity of specific transcription factors, such as MXI1, E2F1, ATF5, and ASCL1, and regulates the expression of cell cycle–associated genes along with related signaling pathways, like the Wnt/β-catenin axis. Moreover, it can interact with specific miRNAs, including miR-326, miR-141, miR-148b-3p, miR-15b, and miR-126-5p. Of importance, HOTAIR has been demonstrated to enhance angiogenesis and affect the permeability of the blood–tumor barrier, thus modulating the efficacy of chemotherapeutic agents. Herein, we provide evidence on the functional role of HOTAIR in gliomas and discuss the benefits of its targeting as a novel approach toward glioma treatment.

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Abbreviations

HOTAIR:

HOX transcript antisense intergenic RNA

ASCL1:

Achaete-scute homolog 1

ATF5:

Activating transcription factor 5

APC:

Adenomatous polyposis coli

ANRIL:

Antisense ncRNA in the INK4 locus

Bcl-xL:

B cell lymphoma-extra-large

BET:

Bromodomain and extraterminal

BRD4:

Bromodomain containing 4

SNORD76:

C/D box snoRNA U76

CCLE:

Cancer Cell Line Encyclopedia

CNS:

Central nervous system

CGGA:

Chinese Glioma Genome Atlas

CD300A:

Cluster of differentiation 300A

CRNDE:

Colorectal neoplasia differentially expressed

CDK2:

Cyclin-dependent kinase 2

CDK4:

Cyclin-dependent kinase 4

H3K4me2:

Dimethylation of histone 3 lysine 4

ADAM22:

Disintegrin and metalloproteinase domain-containing protein 22

EED:

Embryonic ectoderm development

EZH2:

Enhancer of zeste homolog 2

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial–mesenchymal transition

FGF1:

Fibroblast growth factor 1

FGFR:

Fibroblast growth factor receptor

GSEA:

Gene set enrichment analysis

GWAS:

Genome-wide association studies

GSCs:

Glioma stem cells

GSH:

Glutathione

GSK3β:

Glycogen synthase kinase-3β

GAS5:

Growth arrest-specific 5

HDAC1:

Histone deacetylase 1

HIF-1:

Hypoxia-inducible factor-1

IGF1R:

Insulin-like growth factor receptor-1

IDH:

Isocitrate dehydrogenase

KRAS:

Kirsten rat sarcoma viral oncogene

STAT3:

Signal transducer and activator of transcription 3

lncRNAs:

Long ncRNAs

LRP6:

Low-density lipoprotein receptor-related protein 6

LSD1:

Lysine-specific demethylase 1

mTOR:

Mammalian target of rapamycin

MEG3:

Maternally expressed gene 3

MXI1:

MAX-interacting protein 1

MMPs:

Metalloproteinases

miRNAs:

MicroRNAs

MEK:

Mitogen-activated protein kinase kinase

NLK:

Nemo-like kinase

NCAM1:

Neural cell adhesion molecule 1

TNM:

Node and metastasis

ncRNAs:

Noncoding RNAs

PTCSC3:

Papillary thyroid carcinoma susceptibility candidate 3

PI3K:

Phosphoinositide 3-kinase

piRNAs:

Piwi-interacting RNAs

PRC2:

Polycomb-repressive complex 2

PDCD4:

Programmed cell death protein 4

AKT:

Protein kinase B

PKC:

Protein kinase C

PRKCE:

Protein kinase C epsilon type

qRT-PCR:

Quantitative real-time PCR

REST:

RE1-silencing transcription factor

CoREST1:

REST corepressor 1

RUNX:

Runt-related transcription factor 1

SNPs:

Single nucleotide polymorphisms

siRNAs:

Small interfering RNAs

snRNAs:

Small nuclear RNAs

snoRNAs:

Small nucleolar RNAs

SPION:

Superparamagnetic iron oxide nanoparticles

SUZ12:

Suppressor of zeste homolog 12

TUG1:

Taurine upregulated gene 1

TCGA:

The Cancer Genome Atlas

H3K27me3:

Trimethylation of lysine 27 on histone H3

USF1:

Upstream stimulating factor 1

VEGF:

Vascular endothelial growth factor

WHO:

World Health Organization

References

  1. Bush NA, Chang SM, Berger MS (2017) Current and future strategies for treatment of glioma. Neurosurg Rev 40:1–14

    Google Scholar 

  2. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    CAS  Google Scholar 

  3. Angelopoulou E, Piperi C (2018) Emerging role of plexins signaling in glioma progression and therapy. Cancer Lett 414:81–87

    CAS  Google Scholar 

  4. Wesseling P, Capper D (2018) WHO 2016 classification of gliomas. Neuropathol Appl Neurobiol 44:139–150

    CAS  Google Scholar 

  5. Masui K, Mischel PS, Reifenberger G (2016) Molecular classification of gliomas. Handb Clin Neurol 134:97–120

    Google Scholar 

  6. Angelopoulou E, Paudel YN, Piperi C (2019) Emerging pathogenic and prognostic significance of paired box 3 (PAX3) protein in adult gliomas. Transl Oncol 12:1357–1363

    Google Scholar 

  7. Consortium EP (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74

    Google Scholar 

  8. Gomes AQ, Nolasco S, Soares H (2013) Non-coding RNAs: multi-tasking molecules in the cell. Int J Mol Sci 14:16010–16039

    Google Scholar 

  9. Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159

    CAS  Google Scholar 

  10. Liu SJ, Nowakowski TJ, Pollen AA, Lui JH, Horlbeck MA, Attenello FJ, He D, Weissman JS, Kriegstein AR, Diaz AA et al (2016) Single-cell analysis of long non-coding RNAs in the developing human neocortex. Genome Biol 17:67

    Google Scholar 

  11. Geisler S, Coller J (2013) RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol 14:699–712

    CAS  Google Scholar 

  12. Moran VA, Perera RJ, Khalil AM (2012) Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res 40:6391–6400

    CAS  Google Scholar 

  13. Dong X, Jin Z, Chen Y, Xu H, Ma C, Hong X, Li Y, Zhao G (2018) Knockdown of long non-coding RNA ANRIL inhibits proliferation, migration, and invasion but promotes apoptosis of human glioma cells by upregulation of miR-34a. J Cell Biochem 119:2708–2718

    CAS  Google Scholar 

  14. Zhen L, Yun-Hui L, Hong-Yu D, Jun M, Yi-Long Y (2016) Long noncoding RNA NEAT1 promotes glioma pathogenesis by regulating miR-449b-5p/c-met axis. Tumour Biol 37:673–683

    Google Scholar 

  15. Wang P, Ren Z, Sun P (2012) Overexpression of the long non-coding RNA MEG3 impairs in vitro glioma cell proliferation. J Cell Biochem 113:1868–1874

    CAS  Google Scholar 

  16. Qin N, Tong GF, Sun LW, Xu XL (2017) Long noncoding RNA MEG3 suppresses glioma cell proliferation, migration, and invasion by acting as a competing endogenous RNA of miR-19a. Oncol Res 25:1471–1478

    Google Scholar 

  17. Gong X, Huang MY (2020) Tumor-suppressive function of lncRNA-MEG3 in glioma cells by regulating miR-6088/SMARCB1 axis. Biomed Res Int 2020:4309161

    Google Scholar 

  18. Shang C, Guo Y, Hong Y, Xue YX (2016) Long non-coding RNA TUSC7, a target of miR-23b, plays tumor-suppressing roles in human gliomas. Front Cell Neurosci 10:235

    Google Scholar 

  19. Bhan A, Mandal SS (2015) LncRNA HOTAIR: a master regulator of chromatin dynamics and cancer. Biochim Biophys Acta 1856:151–164

    CAS  Google Scholar 

  20. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL et al (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076

    CAS  Google Scholar 

  21. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A et al (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 106:11667–11672

    CAS  Google Scholar 

  22. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–693

    CAS  Google Scholar 

  23. Tan SK, Pastori C, Penas C, Komotar RJ, Ivan ME, Wahlestedt C, Ayad NG (2018) Serum long noncoding RNA HOTAIR as a novel diagnostic and prognostic biomarker in glioblastoma multiforme. Mol Cancer 17:74

    Google Scholar 

  24. Mozdarani H, Ezzatizadeh V, Rahbar Parvaneh R (2020) The emerging role of the long non-coding RNA HOTAIR in breast cancer development and treatment. J Transl Med 18:152

    CAS  Google Scholar 

  25. Carrion K, Dyo J, Patel V, Sasik R, Mohamed SA, Hardiman G, Nigam V (2014) The long non-coding HOTAIR is modulated by cyclic stretch and WNT/beta-CATENIN in human aortic valve cells and is a novel repressor of calcification genes. PLoS One 9:e96577

    Google Scholar 

  26. Yoon JH, Abdelmohsen K, Kim J, Yang X, Martindale JL, Tominaga-Yamanaka K, White EJ, Orjalo AV, Rinn JL, Kreft SG et al (2013) Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination. Nat Commun 4:2939

    Google Scholar 

  27. Xia M, Yao L, Zhang Q, Wang F, Mei H, Guo X, Huang W (2017) Long noncoding RNA HOTAIR promotes metastasis of renal cell carcinoma by up-regulating histone H3K27 demethylase JMJD3. Oncotarget 8:19795–19802

    Google Scholar 

  28. Zhong DN, Luo YH, Mo WJ, Zhang X, Tan Z, Zhao N, Pang SM, Chen G, Rong MH, Tang W (2018) High expression of long noncoding HOTAIR correlated with hepatocarcinogenesis and metastasis. Mol Med Rep 17:1148–1156

    CAS  Google Scholar 

  29. Lu R, Zhang J, Zhang W, Huang Y, Wang N, Zhang Q, Qu S (2018) Circulating HOTAIR expression predicts the clinical response to neoadjuvant chemotherapy in patients with breast cancer. Cancer Biomark 22:249–256

    Google Scholar 

  30. Yan TH, Lu SW, Huang YQ, Que GB, Chen JH, Chen YP, Zhang HB, Liang XL, Jiang JH (2014) Upregulation of the long noncoding RNA HOTAIR predicts recurrence in stage ta/T1 bladder cancer. Tumour Biol 35:10249–10257

    CAS  Google Scholar 

  31. Balci T, Yilmaz Susluer S, Kayabasi C, Ozmen Yelken B, Biray Avci C, Gunduz C (2016) Analysis of dysregulated long non-coding RNA expressions in glioblastoma cells. Gene 590:120–122

    CAS  Google Scholar 

  32. Rynkeviciene R, Simiene J, Strainiene E, Stankevicius V, Usinskiene J, Miseikyte Kaubriene E, Meskinyte I, Cicenas J, Suziedelis K (2018) Non-coding RNAs in glioma. Cancers (Basel) 11. https://doi.org/10.3390/cancers11010017

  33. Li J, Zhu Y, Wang H, Ji X (2018) Targeting long noncoding RNA in glioma: a pathway perspective. Mol Therapy Nucleic Acids 13:431–441

    CAS  Google Scholar 

  34. Malissovas N, Ninou E, Michail A, Politis PK (2019) Targeting long non-coding RNAs in nervous system cancers: new insights in prognosis, diagnosis and therapy. Curr Med Chem 26:5649–5663

    CAS  Google Scholar 

  35. Shi J, Dong B, Cao J, Mao Y, Guan W, Peng Y, Wang S (2017) Long non-coding RNA in glioma: signaling pathways. Oncotarget 8:27582–27592

    Google Scholar 

  36. Liang H, Huang W, Wang Y, Ding L, Zeng L (2019) Overexpression of MiR-146a-5p upregulates lncRNA HOTAIR in triple-negative breast cancer cells and predicts poor prognosis. Technol Cancer Res Treatment 18:1533033819882949

    CAS  Google Scholar 

  37. Dong X, He X, Guan A, Huang W, Jia H, Huang Y, Chen S, Zhang Z, Gao J, Wang H (2019) Long non-coding RNA Hotair promotes gastric cancer progression via miR-217-GPC5 axis. Life Sci 217:271–282

    CAS  Google Scholar 

  38. Wu Y, Liu J, Zheng Y, You L, Kuang D, Liu T (2014) Suppressed expression of long non-coding RNA HOTAIR inhibits proliferation and tumourigenicity of renal carcinoma cells. Tumour Biol 35:11887–11894

    CAS  Google Scholar 

  39. Ke J, Yao YL, Zheng J, Wang P, Liu YH, Ma J, Li Z, Liu XB, Li ZQ, Wang ZH et al (2015) Knockdown of long non-coding RNA HOTAIR inhibits malignant biological behaviors of human glioma cells via modulation of miR-326. Oncotarget 6:21934–21949

    Google Scholar 

  40. Pastori C, Kapranov P, Penas C, Peschansky V, Volmar CH, Sarkaria JN, Bregy A, Komotar R, St Laurent G, Ayad NG et al (2015) The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation. Proc Natl Acad Sci U S A 112:8326–8331

    CAS  Google Scholar 

  41. Zhang K, Sun X, Zhou X, Han L, Chen L, Shi Z, Zhang A, Ye M, Wang Q, Liu C et al (2015) Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner. Oncotarget 6:537–546

    Google Scholar 

  42. Zhou X, Ren Y, Zhang J, Zhang C, Zhang K, Han L, Kong L, Wei J, Chen L, Yang J et al (2015) HOTAIR is a therapeutic target in glioblastoma. Oncotarget 6:8353–8365

    Google Scholar 

  43. Chen L, Han L, Wei J, Zhang K, Shi Z, Duan R, Li S, Zhou X, Pu P, Zhang J et al (2015) SNORD76, a box C/D snoRNA, acts as a tumor suppressor in glioblastoma. Sci Rep 5:8588

    CAS  Google Scholar 

  44. Chen Y, Bian Y, Zhao S, Kong F, Li X (2016) Suppression of PDCD4 mediated by the long non-coding RNA HOTAIR inhibits the proliferation and invasion of glioma cells. Oncol Lett 12:5170–5176

    CAS  Google Scholar 

  45. Wang G, Li Z, Tian N, Han L, Fu Y, Guo Z, Tian Y (2016) miR-148b-3p inhibits malignant biological behaviors of human glioma cells induced by high HOTAIR expression. Oncol Lett 12:879–886

    CAS  Google Scholar 

  46. Li Y, Wang Z, Wang Y, Zhao Z, Zhang J, Lu J, Xu J, Li X (2016) Identification and characterization of lncRNA mediated transcriptional dysregulation dictates lncRNA roles in glioblastoma. Oncotarget 7:45027–45041

    Google Scholar 

  47. Fang K, Liu P, Dong S, Guo Y, Cui X, Zhu X, Li X, Jiang L, Liu T, Wu Y (2016) Magnetofection based on superparamagnetic iron oxide nanoparticle-mediated low lncRNA HOTAIR expression decreases the proliferation and invasion of glioma stem cells. Int J Oncol 49:509–518

    CAS  Google Scholar 

  48. Bian EB, Ma CC, He XJ, Wang C, Zong G, Wang HL, Zhao B (2016) Epigenetic modification of miR-141 regulates SKA2 by an endogenous ‘sponge’ HOTAIR in glioma. Oncotarget 7:30610–30625

    Google Scholar 

  49. Huang K, Sun J, Yang C, Wang Y, Zhou B, Kang C, Han L, Wang Q (2017) HOTAIR upregulates an 18-gene cell cycle-related mRNA network in glioma. Int J Oncol. https://doi.org/10.3892/ijo.2017.3901

  50. Sa L, Li Y, Zhao L, Liu Y, Wang P, Liu L, Li Z, Ma J, Cai H, Xue Y (2017) The role of HOTAIR/miR-148b-3p/USF1 on regulating the permeability of BTB. Front Mol Neurosci 10:194

    Google Scholar 

  51. Jiang Y, Zhang Q, Bao J, Du C, Wang J, Tong Q, Liu C (2017) Schisandrin B inhibits the proliferation and invasion of glioma cells by regulating the HOTAIR-micoRNA-125a-mTOR pathway. Neuroreport 28:93–100

    CAS  Google Scholar 

  52. Ma MZ, Li CX, Zhang Y, Weng MZ, Zhang MD, Qin YY, Gong W, Quan ZW (2014) Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer. Mol Cancer 13:156

    Google Scholar 

  53. Xavier-Magalhaes A, Oliveira AI, de Castro JV, Pojo M, Goncalves CS, Lourenco T, Viana-Pereira M, Costa S, Linhares P, Vaz R et al (2017) Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosis. J Neuro-Oncol 132:27–34

    CAS  Google Scholar 

  54. Xavier-Magalhaes A, Goncalves CS, Fogli A, Lourenco T, Pojo M, Pereira B, Rocha M, Lopes MC, Crespo I, Rebelo O et al (2018) The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma. Oncotarget 9:15740–15756

    Google Scholar 

  55. Sun G, Wang Y, Zhang J, Lin N, You Y (2018) MiR-15b/HOTAIR/p53 form a regulatory loop that affects the growth of glioma cells. J Cell Biochem 119:4540–4547

    CAS  Google Scholar 

  56. Liu L, Cui S, Wan T, Li X, Tian W, Zhang R, Luo L, Shi Y (2018) Long non-coding RNA HOTAIR acts as a competing endogenous RNA to promote glioma progression by sponging miR-126-5p. J Cell Physiol 233:6822–6831

    CAS  Google Scholar 

  57. Liu Y, Jiang H, Zhou H, Ying X, Wang Z, Yang Y, Xu W, He X, Li Y (2018) Lentivirus-mediated silencing of HOTAIR lncRNA restores gefitinib sensitivity by activating Bax/Caspase-3 and suppressing TGF-alpha/EGFR signaling in lung adenocarcinoma. Oncol Lett 15:2829–2838

    Google Scholar 

  58. Yang B, Wei ZY, Wang BQ, Yang HC, Wang JY, Bu XY (2018) Down-regulation of the long noncoding RNA-HOX transcript antisense intergenic RNA inhibits the occurrence and progression of glioma. J Cell Biochem 119:2278–2287

    CAS  Google Scholar 

  59. Lei B, Yu L, Jung TA, Deng Y, Xiang W, Liu Y, Qi S (2018) Prospective series of nine long noncoding RNAs associated with survival of patients with glioblastoma. J Neurol Surg Part A 79:471–478

    Google Scholar 

  60. Shen J, Hodges TR, Song R, Gong Y, Calin GA, Heimberger AB, Zhao H (2018) Serum HOTAIR and GAS5 levels as predictors of survival in patients with glioblastoma. Mol Carcinog 57:137–141

    CAS  Google Scholar 

  61. Li Z, Tan H, Zhao W, Xu Y, Zhang Z, Wang M, Zhou X (2019a) Integrative analysis of DNA methylation and gene expression profiles identifies MIR4435-2HG as an oncogenic lncRNA for glioma progression. Gene 715:144012

    CAS  Google Scholar 

  62. Li Y, Ren Y, Wang Y, Tan Y, Wang Q, Cai J, Zhou J, Yang C, Zhao K, Yi K et al (2019b) A compound AC1Q3QWB selectively disrupts HOTAIR-mediated recruitment of PRC2 and enhances cancer therapy of DZNep. Theranostics 9:4608–4623

    CAS  Google Scholar 

  63. Zhao WH, Yuan HY, Ren XY, Huang K, Guo ZY (2019a) Association between expression of HOTAIR and invasiveness of gliomas, and its predictive value. Adv Clin Exp Med 28:1179–1183

    Google Scholar 

  64. Zhao K, Cui X, Wang Q, Fang C, Tan Y, Wang Y, Yi K, Yang C, You H, Shang R et al (2019b) RUNX1 contributes to the mesenchymal subtype of glioblastoma in a TGFbeta pathway-dependent manner. Cell Death Dis 10:877

    CAS  Google Scholar 

  65. Shi J, Lv S, Wu M, Wang X, Deng Y, Li Y, Li K, Zhao H, Zhu X, Ye M (2020) HOTAIR-EZH2 inhibitor AC1Q3QWB upregulates CWF19L1 and enhances cell cycle inhibition of CDK4/6 inhibitor palbociclib in glioma. Clin Translat Med 10:182–198

    Google Scholar 

  66. Zhang L, He A, Chen B, Bi J, Chen J, Guo D, Qian Y, Wang W, Shi T, Zhao Z et al (2020) A HOTAIR regulatory element modulates glioma cell sensitivity to temozolomide through long-range regulation of multiple target genes. Genome Res. https://doi.org/10.1101/gr.251058.119

  67. Zhang J, Chen G, Gao Y, Liang H (2020) HOTAIR/miR-125 axis-mediated hexokinase 2 expression promotes chemoresistance in human glioblastoma. J Cell Mol Med 24:5707–5717

    CAS  Google Scholar 

  68. Yuan Z, Yang Z, Li W, Wu A, Su Z, Jiang B (2020) Exosome-mediated transfer of long noncoding RNA HOTAIR regulates temozolomide resistance by miR-519a-3p/RRM1 axis in glioblastoma. Cancer Biother Radiopharm. https://doi.org/10.1089/cbr.2019.3499

  69. Li H, Guan C (2020) HOTAIR inhibits the proliferation of glioblastoma cells by targeting miR-219. Cancer Biomark 28:41–47

    CAS  Google Scholar 

  70. Lu L, Zhu G, Zhang C, Deng Q, Katsaros D, Mayne ST, Risch HA, Mu L, Canuto EM, Gregori G et al (2012) Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer. Breast Cancer Res Treat 136:875–883

    CAS  Google Scholar 

  71. Hajjari M, Salavaty A (2015) HOTAIR: an oncogenic long non-coding RNA in different cancers. Cancer Biol Med 12:1–9

    CAS  Google Scholar 

  72. Bhan A, Hussain I, Ansari KI, Bobzean SA, Perrotti LI, Mandal SS (2014) Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo. J Steroid Biochem Mol Biol 141:160–170

    CAS  Google Scholar 

  73. Padua Alves C, Fonseca AS, Muys BR, de Barros ELBR, Burger MC, de Souza JE, Valente V, Zago MA, Silva WA Jr (2013) Brief report: the lincRNA Hotair is required for epithelial-to-mesenchymal transition and stemness maintenance of cancer cell lines. Stem Cells 31:2827–2832

    Google Scholar 

  74. Zhuang Y, Wang X, Nguyen HT, Zhuo Y, Cui X, Fewell C, Flemington EK, Shan B (2013) Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen. J Hematol Oncol 6:35

    CAS  Google Scholar 

  75. Cancer Genome Atlas Research N (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068

    Google Scholar 

  76. Pojo M, Goncalves CS, Xavier-Magalhaes A, Oliveira AI, Goncalves T, Correia S, Rodrigues AJ, Costa S, Pinto L, Pinto AA et al (2015) A transcriptomic signature mediated by HOXA9 promotes human glioblastoma initiation, aggressiveness and resistance to temozolomide. Oncotarget 6:7657–7674

    Google Scholar 

  77. Wang J, Wang H, Li Z, Wu Q, Lathia JD, McLendon RE, Hjelmeland AB, Rich JN (2008) c-Myc is required for maintenance of glioma cancer stem cells. PLoS One 3:e3769

    Google Scholar 

  78. Kaminska B, Kocyk M, Kijewska M (2013) TGF beta signaling and its role in glioma pathogenesis. Adv Exp Med Biol 986:171–187

    CAS  Google Scholar 

  79. Zhang JX, Han L, Bao ZS, Wang YY, Chen LY, Yan W, Yu SZ, Pu PY, Liu N, You YP et al (2013) HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma. Neuro-Oncology 15:1595–1603

    CAS  Google Scholar 

  80. Wenzel ES, Singh ATK (2018) Cell-cycle checkpoints and aneuploidy on the path to cancer. In Vivo 32:1–5

    CAS  Google Scholar 

  81. Fischer M, Quaas M, Steiner L, Engeland K (2016) The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes. Nucleic Acids Res 44:164–174

    CAS  Google Scholar 

  82. Ohta S, Kimura M, Takagi S, Toramoto I, Ishihama Y (2016) Identification of mitosis-specific phosphorylation in mitotic chromosome-associated proteins. J Proteome Res 15:3331–3341

    CAS  Google Scholar 

  83. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RG, Otte AP et al (2002) The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419:624–629

    CAS  Google Scholar 

  84. Orzan F, Pellegatta S, Poliani PL, Pisati F, Caldera V, Menghi F, Kapetis D, Marras C, Schiffer D, Finocchiaro G (2011) Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells. Neuropathol Appl Neurobiol 37:381–394

    CAS  Google Scholar 

  85. Suva ML, Riggi N, Janiszewska M, Radovanovic I, Provero P, Stehle JC, Baumer K, Le Bitoux MA, Marino D, Cironi L et al (2009) EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Res 69:9211–9218

    CAS  Google Scholar 

  86. Zhang R, Wang R, Chang H, Wu F, Liu C, Deng D, Fan W (2012) Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest in the G0/G1 phase and apoptosis in U87 human glioma cells. Oncol Rep 28:2278–2284

    CAS  Google Scholar 

  87. Kim E, Kim M, Woo DH, Shin Y, Shin J, Chang N, Oh YT, Kim H, Rheey J, Nakano I et al (2013) Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells. Cancer Cell 23:839–852

    CAS  Google Scholar 

  88. Liu H, Sun Y, Qi X, Gordon RE, O'Brien JA, Yuan H, Zhang J, Wang Z, Zhang M, Song Y et al (2019) EZH2 phosphorylation promotes self-renewal of glioma stem-like cells through NF-kappaB methylation. Front Oncol 9:641

    Google Scholar 

  89. Zhang K, Zhang J, Han L, Pu P, Kang C (2012) Wnt/beta-catenin signaling in glioma. J Neuroimmune Pharmacol 7:740–749

    Google Scholar 

  90. Liu HW, Su YK, Bamodu OA, Hueng DY, Lee WH, Huang CC, Deng L, Hsiao M, Chien MH, Yeh CT et al (2018) The disruption of the beta-catenin/TCF-1/STAT3 signaling axis by 4-acetylantroquinonol B inhibits the tumorigenesis and cancer stem-cell-like properties of glioblastoma cells, in vitro and in vivo cancers. Cancers (Basel) 10. https://doi.org/10.3390/cancers10120491

  91. Ishitani T, Ninomiya-Tsuji J, Nagai S, Nishita M, Meneghini M, Barker N, Waterman M, Bowerman B, Clevers H, Shibuya H et al (1999) The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF. Nature 399:798–802

    CAS  Google Scholar 

  92. Gan HK, Kaye AH, Luwor RB (2009) The EGFRvIII variant in glioblastoma multiforme. J Clin Neurosci 16:748–754

    CAS  Google Scholar 

  93. Heimberger AB, Hlatky R, Suki D, Yang D, Weinberg J, Gilbert M, Sawaya R, Aldape K (2005) Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res 11:1462–1466

    CAS  Google Scholar 

  94. Bae GY, Choi SJ, Lee JS, Jo J, Lee J, Kim J, Cha HJ (2013) Loss of E-cadherin activates EGFR-MEK/ERK signaling, which promotes invasion via the ZEB1/MMP2 axis in non-small cell lung cancer. Oncotarget 4:2512–2522

    Google Scholar 

  95. Wang Y, Lin Z, Sun L, Fan S, Huang Z, Zhang D, Yang Z, Li J, Chen W (2014) Akt/Ezrin Tyr353/NF-kappaB pathway regulates EGF-induced EMT and metastasis in tongue squamous cell carcinoma. Br J Cancer 110:695–705

    CAS  Google Scholar 

  96. Vesuna F, van Diest P, Chen JH, Raman V (2008) Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer. Biochem Biophys Res Commun 367:235–241

    CAS  Google Scholar 

  97. Jia L, Tian Y, Chen Y, Zhang G (2018) The silencing of LncRNA-H19 decreases chemoresistance of human glioma cells to temozolomide by suppressing epithelial-mesenchymal transition via the Wnt/beta-catenin pathway. OncoTargets Therapy 11:313–321

    Google Scholar 

  98. Xia S, Ji R, Zhan W (2017) Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) inhibits proliferation and invasion of glioma cells by suppressing the Wnt/beta-catenin signaling pathway. BMC Neurol 17:30

    Google Scholar 

  99. Xiao D, Cui X, Wang X (2019) LncRNA PTCSC3 inhibits cell proliferation in laryngeal squamous cell carcinoma by down-regulating lncRNA HOTAIR. Biosci Rep 39. https://doi.org/10.1042/BSR20182362

  100. Liwak U, Jordan LE, Von-Holt SD, Singh P, Hanson JE, Lorimer IA, Roncaroli F, Holcik M (2013) Loss of PDCD4 contributes to enhanced chemoresistance in glioblastoma multiforme through de-repression of Bcl-xL translation. Oncotarget 4:1365–1372

    Google Scholar 

  101. Gaur AB, Holbeck SL, Colburn NH, Israel MA (2011) Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo. Neuro-oncology 13:580–590

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  103. Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, Dorrestein PC, Rosenfeld MG (2011) ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell 147:773–788

    CAS  Google Scholar 

  104. Manni I, Tunici P, Cirenei N, Albarosa R, Colombo BM, Roz L, Sacchi A, Piaggio G, Finocchiaro G (2002) Mxi1 inhibits the proliferation of U87 glioma cells through down-regulation of cyclin B1 gene expression. Br J Cancer 86:477–484

    CAS  Google Scholar 

  105. Xu S, Wen Z, Jiang Q, Zhu L, Feng S, Zhao Y, Wu J, Dong Q, Mao J, Zhu Y (2015) CD58, a novel surface marker, promotes self-renewal of tumor-initiating cells in colorectal cancer. Oncogene 34:1520–1531

    CAS  Google Scholar 

  106. Sharif TR, Sharif M (1999) Overexpression of protein kinase C epsilon in astroglial brain tumor derived cell lines and primary tumor samples. Int J Oncol 15:237–243

    CAS  Google Scholar 

  107. Safaee M, Clark AJ, Oh MC, Ivan ME, Bloch O, Kaur G, Sun MZ, Kim JM, Oh T, Berger MS et al (2013) Overexpression of CD97 confers an invasive phenotype in glioblastoma cells and is associated with decreased survival of glioblastoma patients. PLoS One 8:e62765

    Google Scholar 

  108. Angelastro JM, Canoll PD, Kuo J, Weicker M, Costa A, Bruce JN, Greene LA (2006) Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. Oncogene 25:907–916

    CAS  Google Scholar 

  109. Wang Z, Dai X, Chen Y, Sun C, Zhu Q, Zhao H, Liu G, Huang Q, Lan Q (2015) MiR-30a-5p is induced by Wnt/beta-catenin pathway and promotes glioma cell invasion by repressing NCAM. Biochem Biophys Res Commun 465:374–380

    CAS  Google Scholar 

  110. D'Abaco GM, Ng K, Paradiso L, Godde NJ, Kaye A, Novak U (2006) ADAM22, expressed in normal brain but not in high-grade gliomas, inhibits cellular proliferation via the disintegrin domain. Neurosurgery 58:179–186; discussion 179-186

    Google Scholar 

  111. Park NI, Guilhamon P, Desai K, McAdam RF, Langille E, O'Connor M, Lan X, Whetstone H, Coutinho FJ, Vanner RJ et al (2017) ASCL1 reorganizes chromatin to direct neuronal fate and suppress tumorigenicity of glioblastoma stem cells. Cell Stem Cell 21(209–224):e207

    Google Scholar 

  112. Xiao D, Huang J, Pan Y, Li H, Fu C, Mao C, Cheng Y, Shi Y, Chen L, Jiang Y et al (2017) Chromatin remodeling factor LSH is upregulated by the LRP6-GSK3beta-E2F1 axis linking reversely with survival in gliomas. Theranostics 7:132–143

    CAS  Google Scholar 

  113. Suzuki N, Idogawa M, Tange S, Ohashi T, Sasaki Y, Nakase H, Tokino T (2020) p53-induced ARVCF modulates the splicing landscape and supports the tumor suppressive function of p53. Oncogene 39:2202–2211

    CAS  Google Scholar 

  114. Zhi T, Jiang K, Xu X, Yu T, Zhou F, Wang Y, Liu N, Zhang J (2019) ECT2/PSMD14/PTTG1 axis promotes the proliferation of glioma through stabilizing E2F1. Neuro-oncology 21:462–473

    CAS  Google Scholar 

  115. Held-Feindt J, Hattermann K, Knerlich-Lukoschus F, Mehdorn HM, Mentlein R (2011) SP100 reduces malignancy of human glioma cells. Int J Oncol 38:1023–1030

    CAS  Google Scholar 

  116. Bogoch Y, Friedlander-Malik G, Lupu L, Bondar E, Zohar N, Langier S, Ram Z, Nachmany I, Klausner JM, Pencovich N (2017) Augmented expression of RUNX1 deregulates the global gene expression of U87 glioblastoma multiforme cells and inhibits tumor growth in mice. Tumour Biol 39:1010428317698357

    Google Scholar 

  117. Yoon JH, Abdelmohsen K, Gorospe M (2014) Functional interactions among microRNAs and long noncoding RNAs. Semin Cell Dev Biol 34:9–14

    CAS  Google Scholar 

  118. Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, Kong R, Xia R, Lu KH, Li JH et al (2014) Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer 13:92

    CAS  Google Scholar 

  119. Zhang H, Cai K, Wang J, Wang X, Cheng K, Shi F, Jiang L, Zhang Y, Dou J (2014) MiR-7, inhibited indirectly by lincRNA HOTAIR, directly inhibits SETDB1 and reverses the EMT of breast cancer stem cells by downregulating the STAT3 pathway. Stem Cells 32:2858–2868

    CAS  Google Scholar 

  120. Kefas B, Comeau L, Erdle N, Montgomery E, Amos S, Purow B (2010) Pyruvate kinase M2 is a target of the tumor-suppressive microRNA-326 and regulates the survival of glioma cells. Neuro-oncology 12:1102–1112

    CAS  Google Scholar 

  121. Hsu YC, Kao CY, Chung YF, Lee DC, Liu JW, Chiu IM (2016) Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells. Exp Cell Res 344:153–166

    CAS  Google Scholar 

  122. Xin Z, Song X, Jiang B, Gongsun X, Song L, Qin Q, Wang Q, Shi M, Liu X (2018) Blocking FGFR4 exerts distinct anti-tumorigenic effects in esophageal squamous cell carcinoma. Thoracic Cancer 9:1687–1698

    CAS  Google Scholar 

  123. Packer LM, Geng X, Bonazzi VF, Ju RJ, Mahon CE, Cummings MC, Stephenson SA, Pollock PM (2017) PI3K inhibitors synergize with FGFR inhibitors to enhance antitumor responses in FGFR2(mutant) endometrial cancers. Mol Cancer Ther 16:637–648

    CAS  Google Scholar 

  124. Zanotto-Filho A, Goncalves RM, Klafke K, de Souza PO, Dillenburg FC, Carro L, Gelain DP, Moreira JC (2017) Inflammatory landscape of human brain tumors reveals an NFkappaB dependent cytokine pathway associated with mesenchymal glioblastoma. Cancer Lett 390:176–187

    CAS  Google Scholar 

  125. Chiyomaru T, Yamamura S, Fukuhara S, Yoshino H, Kinoshita T, Majid S, Saini S, Chang I, Tanaka Y, Enokida H et al (2013) Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR. PLoS One 8:e70372

    CAS  Google Scholar 

  126. Chiyomaru T, Fukuhara S, Saini S, Majid S, Deng G, Shahryari V, Chang I, Tanaka Y, Enokida H, Nakagawa M et al (2014) Long non-coding RNA HOTAIR is targeted and regulated by miR-141 in human cancer cells. J Biol Chem 289:12550–12565

    CAS  Google Scholar 

  127. Hanisch A, Sillje HH, Nigg EA (2006) Timely anaphase onset requires a novel spindle and kinetochore complex comprising Ska1 and Ska2. EMBO J 25:5504–5515

    CAS  Google Scholar 

  128. He XJ, Bian EB, Ma CC, Wang C, Wang HL, Zhao B (2018) Long non-coding RNA SPRY4-IT1 promotes the proliferation and invasion of U251 cells through upregulation of SKA2. Oncol Lett 15:3977–3984

    Google Scholar 

  129. Zhao G, Zhang JG, Liu Y, Qin Q, Wang B, Tian K, Liu L, Li X, Niu Y, Deng SC et al (2013) miR-148b functions as a tumor suppressor in pancreatic cancer by targeting AMPKalpha1. Mol Cancer Ther 12:83–93

    CAS  Google Scholar 

  130. Chang H, Zhou X, Wang ZN, Song YX, Zhao F, Gao P, Chiang Y, Xu HM (2012) Increased expression of miR-148b in ovarian carcinoma and its clinical significance. Mol Med Rep 5:1277–1280

    CAS  Google Scholar 

  131. Wang J, Liu H, Tian L, Wang F, Han L, Zhang W, Bai YA (2017) miR-15b inhibits the progression of glioblastoma cells through targeting insulin-like growth factor receptor 1. Hormones Cancer 8:49–57

    CAS  Google Scholar 

  132. Zhang Y, Dube C, Gibert M Jr, Cruickshanks N, Wang B, Coughlan M, Yang Y, Setiady I, Deveau C, Saoud K et al (2018) The p53 pathway in glioblastoma. Cancers 10. https://doi.org/10.3390/cancers10090297

  133. Szeliga M, Albrecht J (2015) Opposing roles of glutaminase isoforms in determining glioblastoma cell phenotype. Neurochem Int 88:6–9

    CAS  Google Scholar 

  134. Petovari G, Danko T, Krencz I, Hujber Z, Rajnai H, Vetlenyi E, Raffay R, Papay J, Jeney A, Sebestyen A (2019) Inhibition of metabolic shift can decrease therapy resistance in human high-grade glioma cells. Pathol Oncol Res. https://doi.org/10.1007/s12253-019-00677-2

  135. Luan Y, Zuo L, Zhang S, Wang G, Peng T (2015) MicroRNA-126 acts as a tumor suppressor in glioma cells by targeting insulin receptor substrate 1 (IRS-1). Int J Clin Exp Pathol 8:10345–10354

    CAS  Google Scholar 

  136. Li Y, Li Y, Ge P, Ma C (2017) MiR-126 regulates the ERK pathway via targeting KRAS to inhibit the glioma cell proliferation and invasion. Mol Neurobiol 54:137–145

    CAS  Google Scholar 

  137. Jiang Y, Zhang Q, Bao J, Du C, Wang J, Tong Q, Liu C (2015) Schisandrin B suppresses glioma cell metastasis mediated by inhibition of mTOR/MMP-9 signal pathway. Biomed Pharmacotherapy 74:77–82

    CAS  Google Scholar 

  138. Yuan J, Xiao G, Peng G, Liu D, Wang Z, Liao Y, Liu Q, Wu M, Yuan X (2015) MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ. Biochem Biophys Res Commun 457:171–176

    CAS  Google Scholar 

  139. Tang L, Shen H, Li X, Li Z, Liu Z, Xu J, Ma S, Zhao X, Bai X, Li M et al (2016) MiR-125a-5p decreases after long non-coding RNA HOTAIR knockdown to promote cancer cell apoptosis by releasing caspase 2. Cell Death Dis 7:e2137

    CAS  Google Scholar 

  140. Rao SA, Arimappamagan A, Pandey P, Santosh V, Hegde AS, Chandramouli BA, Somasundaram K (2013) miR-219-5p inhibits receptor tyrosine kinase pathway by targeting EGFR in glioblastoma. PLoS One 8:e63164

    Google Scholar 

  141. Yoshihama M, Nakao A, Kenmochi N (2013) snOPY: a small nucleolar RNA orthological gene database. BMC Res Notes 6:426

    Google Scholar 

  142. Guarnaccia L, Navone SE, Trombetta E, Cordiglieri C, Cherubini A, Crisa FM, Rampini P, Miozzo M, Fontana L, Caroli M et al (2018) Angiogenesis in human brain tumors: screening of drug response through a patient-specific cell platform for personalized therapy. Sci Rep 8:8748

    Google Scholar 

  143. Plate KH, Breier G, Weich HA, Mennel HD, Risau W (1994) Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. Int J Cancer 59:520–529

    CAS  Google Scholar 

  144. Subramaniam SR, Federoff HJ (2017) Targeting microglial activation states as a therapeutic avenue in Parkinson’s disease. Front Aging Neurosci 9:176

    Google Scholar 

  145. Fu WM, Lu YF, Hu BG, Liang WC, Zhu X, Yang HD, Li G, Zhang JF (2016) Long noncoding RNA Hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways. Oncotarget 7:4712–4723

    Google Scholar 

  146. Kaur B, Khwaja FW, Severson EA, Matheny SL, Brat DJ, Van Meir EG (2005) Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro-oncology 7:134–153

    CAS  Google Scholar 

  147. Hong Q, Li O, Zheng W, Xiao WZ, Zhang L, Wu D, Cai GY, He JC, Chen XM (2017) LncRNA HOTAIR regulates HIF-1alpha/AXL signaling through inhibition of miR-217 in renal cell carcinoma. Cell Death Dis 8:e2772

    CAS  Google Scholar 

  148. Gezer U, Ozgur E, Cetinkaya M, Isin M, Dalay N (2014) Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes. Cell Biol Int 38:1076–1079

    CAS  Google Scholar 

  149. Wang S, Zhang X, Guo Y, Rong H, Liu T (2017) The long noncoding RNA HOTAIR promotes Parkinson's disease by upregulating LRRK2 expression. Oncotarget 8:24449–24456

    Google Scholar 

  150. Pahlevan Kakhki M, Nikravesh A, Shirvani Farsani Z, Sahraian MA, Behmanesh M (2018) HOTAIR but not ANRIL long non-coding RNA contributes to the pathogenesis of multiple sclerosis. Immunology 153:479–487

    CAS  Google Scholar 

  151. Wang W, He X, Zheng Z, Ma X, Hu X, Wu D, Wang M (2017) Serum HOTAIR as a novel diagnostic biomarker for esophageal squamous cell carcinoma. Mol Cancer 16:75

    CAS  Google Scholar 

  152. Gao JZ, Li J, Du JL, Li XL (2016) Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence. Oncol Lett 11:1791–1798

    CAS  Google Scholar 

  153. Liu XH, Liu ZL, Sun M, Liu J, Wang ZX, De W (2013) The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. BMC Cancer 13:464

    Google Scholar 

  154. Sorensen KP, Thomassen M, Tan Q, Bak M, Cold S, Burton M, Larsen MJ, Kruse TA (2013) Long non-coding RNA HOTAIR is an independent prognostic marker of metastasis in estrogen receptor-positive primary breast cancer. Breast Cancer Res Treat 142:529–536

    Google Scholar 

  155. Svoboda M, Slyskova J, Schneiderova M, Makovicky P, Bielik L, Levy M, Lipska L, Hemmelova B, Kala Z, Protivankova M et al (2014) HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients. Carcinogenesis 35:1510–1515

    CAS  Google Scholar 

  156. Xu Z, Chen H, Yang B, Liu X, Zhou X, Kong H (2019) The association of HOTAIR with the diagnosis and prognosis of gastric cancer and its effect on the proliferation of gastric cancer cells. Can J Gastroenterol Hepatol 2019:3076345

    Google Scholar 

  157. Toy HI, Okmen D, Kontou PI, Georgakilas AG, Pavlopoulou A (2019) HOTAIR as a prognostic predictor for diverse human cancers: a meta- and bioinformatics analysis. Cancers (Basel) 11. https://doi.org/10.3390/cancers11060778

  158. Zhang JX, Zhang J, Yan W, Wang YY, Han L, Yue X, Liu N, You YP, Jiang T, Pu PY et al (2013) Unique genome-wide map of TCF4 and STAT3 targets using ChIP-seq reveals their association with new molecular subtypes of glioblastoma. Neuro-oncology 15:279–289

    CAS  Google Scholar 

  159. Zhang C, Moore LM, Li X, Yung WK, Zhang W (2013) IDH1/2 mutations target a key hallmark of cancer by deregulating cellular metabolism in glioma. Neuro-oncology 15:1114–1126

    CAS  Google Scholar 

  160. Li J, Wang Y, Yu J, Dong R, Qiu H (2015) A high level of circulating HOTAIR is associated with progression and poor prognosis of cervical cancer. Tumour Biol 36:1661–1665

    CAS  Google Scholar 

  161. Basu B, Ghosh MK (2019) Extracellular vesicles in glioma: from diagnosis to therapy. BioEssays 41:e1800245

    Google Scholar 

  162. Ghasimi S, Wibom C, Dahlin AM, Brannstrom T, Golovleva I, Andersson U, Melin B (2016) Genetic risk variants in the CDKN2A/B, RTEL1 and EGFR genes are associated with somatic biomarkers in glioma. J Neuro-Oncol 127:483–492

    CAS  Google Scholar 

  163. Vieira de Castro J, Goncalves CS, Costa S, Linhares P, Vaz R, Nabico R, Amorim J, Viana-Pereira M, Reis RM, Costa BM (2015) Impact of TGF-beta1 -509C/T and 869T/C polymorphisms on glioma risk and patient prognosis. Tumour Biol 36:6525–6532

    CAS  Google Scholar 

  164. Bayram S, Sumbul AT, Batmaci CY, Genc A (2015) Effect of HOTAIR rs920778 polymorphism on breast cancer susceptibility and clinicopathologic features in a Turkish population. Tumour Biol 36:3863–3870

    CAS  Google Scholar 

  165. Bayram S, Sumbul AT, Dadas E (2016) A functional HOTAIR rs12826786 C>T polymorphism is associated with breast cancer susceptibility and poor clinicopathological characteristics in a Turkish population: a hospital-based case-control study. Tumour Biol 37:5577–5584

    CAS  Google Scholar 

  166. Zhang X, Zhou L, Fu G, Sun F, Shi J, Wei J, Lu C, Zhou C, Yuan Q, Yang M (2014) The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. Carcinogenesis 35:2062–2067

    CAS  Google Scholar 

  167. Pan W, Liu L, Wei J, Ge Y, Zhang J, Chen H, Zhou L, Yuan Q, Zhou C, Yang M (2016) A functional lncRNA HOTAIR genetic variant contributes to gastric cancer susceptibility. Mol Carcinog 55:90–96

    CAS  Google Scholar 

  168. Guo W, Dong Z, Bai Y, Guo Y, Shen S, Kuang G, Xu J (2015) Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China. Tumour Biol 36:2845–2854

    CAS  Google Scholar 

  169. Mishra S, Verma SS, Rai V, Awasthee N, Chava S, Hui KM, Kumar AP, Challagundla KB, Sethi G, Gupta SC (2019) Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases. Cell Mol Life Sci 76:1947–1966

    CAS  Google Scholar 

  170. Chen J, Lin C, Yong W, Ye Y, Huang Z (2015) Calycosin and genistein induce apoptosis by inactivation of HOTAIR/p-Akt signaling pathway in human breast cancer MCF-7 cells. Cell Physiol Biochem 35:722–728

    CAS  Google Scholar 

  171. Yazdani Y, Sharifi Rad MR, Taghipour M, Chenari N, Ghaderi A, Razmkhah M (2016) Genistein suppression of matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF) expression in mesenchymal stem cell like cells isolated from high and low grade gliomas. Asian Pac J Cancer Prev 17:5303–5307

    Google Scholar 

  172. Yakisich JS, Ohlsson Lindblom I, Siden A, Cruz MH (2009) Rapid inhibition of ongoing DNA synthesis in human glioma tissue by genistein. Oncol Rep 22:569–574

    CAS  Google Scholar 

  173. Imai-Sumida M, Chiyomaru T, Majid S, Saini S, Nip H, Dahiya R, Tanaka Y, Yamamura S (2017) Silibinin suppresses bladder cancer through down-regulation of actin cytoskeleton and PI3K/Akt signaling pathways. Oncotarget 8:92032–92042

    Google Scholar 

  174. Chakrabarti M, Ray SK (2016) Anti-tumor activities of luteolin and silibinin in glioblastoma cells: overexpression of miR-7-1-3p augmented luteolin and silibinin to inhibit autophagy and induce apoptosis in glioblastoma in vivo. Apoptosis 21:312–328

    CAS  Google Scholar 

  175. Kwiatkowska A, Symons M (2020) Signaling determinants of glioma cell invasion. Adv Exp Med Biol 1202:129–149

    CAS  Google Scholar 

  176. Chen H, Xin Y, Zhou L, Huang JM, Tao L, Cheng L, Tian J (2014) Cisplatin and paclitaxel target significant long noncoding RNAs in laryngeal squamous cell carcinoma. Med Oncol 31:246

    Google Scholar 

  177. Li CH, Chen Y (2013) Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol 45:1895–1910

    CAS  Google Scholar 

  178. Jiang MC, Ni JJ, Cui WY, Wang BY, Zhuo W (2019) Emerging roles of lncRNA in cancer and therapeutic opportunities. Am J Cancer Res 9:1354–1366

    CAS  Google Scholar 

  179. Jin L, Wang Q, Chen J, Wang Z, Xin H, Zhang D (2019) Efficient delivery of therapeutic siRNA by Fe3O4 magnetic nanoparticles into oral cancer cells. Pharmaceutics 11. https://doi.org/10.3390/pharmaceutics11110615

  180. Bruniaux J, Allard-Vannier E, Aubrey N, Lakhrif Z, Ben Djemaa S, Eljack S, Marchais H, Herve-Aubert K, Chourpa I, David S (2019) Magnetic nanocarriers for the specific delivery of siRNA: contribution of breast cancer cells active targeting for down-regulation efficiency. Int J Pharm 569:118572

    CAS  Google Scholar 

  181. Sandmann T, Bourgon R, Garcia J, Li C, Cloughesy T, Chinot OL, Wick W, Nishikawa R, Mason W, Henriksson R et al (2015) Patients with proneural glioblastoma may derive overall survival benefit from the addition of bevacizumab to first-line radiotherapy and temozolomide: retrospective analysis of the AVAglio trial. J Clin Oncol 33:2735–2744

    CAS  Google Scholar 

  182. Strepkos D, Markouli M, Klonou A, Piperi C, Papavassiliou AG (2020 Jan) Insights in the immunobiology of glioblastoma. J Mol Med (Berl) 98(1):1–10

    Google Scholar 

  183. Nikaki A, Piperi C, Papavassiliou AG (2012 Oct) Role of microRNAs in gliomagenesis: targeting miRNAs in glioblastoma multiforme therapy. Expert Opin Investig Drugs 21(10):1475–1488

    CAS  Google Scholar 

  184. Paulmurugan R, Malhotra M, Massoud TF (2019 Jul) The protean world of non-coding RNAs in glioblastoma. J Mol Med (Berl) 97(7):909–925

    Google Scholar 

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YNP would like to acknowledge Monash University Malaysia for supporting with HDR Scholarship.

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EA carried out the literature review and conceptualized and prepared the initial draft. YNP edited and contributed in the final manuscript. CP provided critical inputs and edited and contributed to the final version of the manuscript. All authors read and approved the final manuscript.

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Angelopoulou, E., Paudel, Y.N. & Piperi, C. Critical role of HOX transcript antisense intergenic RNA (HOTAIR) in gliomas. J Mol Med 98, 1525–1546 (2020). https://doi.org/10.1007/s00109-020-01984-x

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