MicroRNAs in neuroblastoma tumorigenesis, therapy resistance, and disease evolution

Abstract

Neuroblastoma (NB) deriving from neural crest cells is the most common extra-cranial solid cancer at infancy. NB originates within the peripheral sympathetic ganglia in adrenal medulla and along the midline of the body. Clinically, NB exhibits significant heterogeneity stretching from spontaneous regression to rapid progression to therapy resistance. MicroRNAs (miRNAs, miRs) are small (19-22 nt in length) non-coding RNAs that regulate human gene expression at the post-transcriptional level and are known to regulate cellular signaling, growth, differentiation, death, stemness, and maintenance. Consequently, the function of miRs in tumorigenesis, progression and resistance is of utmost importance for the understanding of dysfunctional cellular pathways that lead to disease evolution, therapy resistance, and poor clinical outcomes. Over the last two decades, much attention has been devoted to understanding the functional roles of miRs in NB biology. This review focuses on highlighting the important implications of miRs within the context of NB disease progression, particularly miRs’ influences on NB disease evolution and therapy resistance. In this review, we discuss the functions of both the “oncomiRs” and “tumor suppressor miRs” in NB progression/therapy resistance. These are the critical components to be considered during the development of novel miR-based therapeutic strategies to counter therapy resistance.

Keywords

miRNAs / progressive neuroblastoma / therapy resistance / oncomiRs / tumor suppressor miRs / tumor progression

References

[1] Marc TG,Smith MA.Sympathetic nervous system tumors. Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995, National Cancer Institute.1999;Bethesda, MDNIH Pub.65-72

[2] Gurney JG,Ross JA.Cancer among infants. Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995, National Cancer Institute.1999;Bethesda, MDNIH Pub.149-56

[3] Morgenstern DA,Irwin MS.Current and future strategies for relapsed neuroblastoma: challenges on the road to precision therapy..J Pediatr Hematol Oncol2013;35:337-47

[4] American-Cancer-Society2013;AtlantaAmerican Cancer Society1-64

[5] Smith MA,Altekruse SF,Melbert DL.Outcomes for children and adolescents with cancer: challenges for the twenty-first century..J Clin Oncol2010;28:2625-34 PMCID:PMC2881732

[6] De Bernardi B,Boni L,Carli M.Disseminated neuroblastoma in children older than one year at diagnosis: comparable results with three consecutive high-dose protocols adopted by the Italian Co-Operative Group for Neuroblastoma..J Clin Oncol2003;21:1592-601

[7] Garaventa A,De Bernardi B,Manzitti C.Outcome of children with neuroblastoma after progression or relapse. A retrospective study of the Italian neuroblastoma registry..Eur J Cancer2009;45:2835-42

[8] London WB,Monclair T,Pearson AD.Clinical and biologic features predictive of survival after relapse of neuroblastoma: a report from the International Neuroblastoma Risk Group project..J Clin Oncol2011;29:3286-92 PMCID:PMC3158599

[9] Maris JM,Bagatell R.Neuroblastoma..Lancet2007;369:2106-20

[10] Grau E,Orellana C,Castel V.There is no evidence that the SDHB gene is involved in neuroblastoma development..Oncol Res2005;15:393-8

[11] Castel V,Canete A,Ruiz A.Neuroblastoma in adolescents: genetic and clinical characterisation..Clin Transl Oncol2010;12:49-54

[12] Fulda S.The PI3K/Akt/mTOR pathway as therapeutic target in neuroblastoma..Curr Cancer Drug Targets2009;9:729-37

[13] Jrebi NY,Joliat GR,Farley DR.Review of our experience with neuroblastoma and ganglioneuroblastoma in adults..World J Surg2014;38:2871-4

[14] Magro G.The glial cell in the ontogenesis of the human peripheral sympathetic nervous system and in neuroblastoma..Pathologica2001;93:505-16

[15] Crane JF.Neural crest stem and progenitor cells..Annu Rev Cell Dev Biol2006;22:267-86

[16] Walton JD,Thomas SK,Guo HF.Characteristics of stem cells from human neuroblastoma cell lines and in tumors..Neoplasia2004;6:838-45 PMCID:PMC1531688

[17] Schwab M.Neuroblastoma - developmental and molecular biology meet therapy design..Cancer Lett2003;197:1

[18] Maris JM.Recent advances in neuroblastoma..N Engl J Med2010;362:2202-11 PMCID:PMC3306838

[19] Cheung NK.Neuroblastoma: developmental biology, cancer genomics and immunotherapy..Nat Rev Cancer2013;13:397-411 PMCID:PMC4386662

[20] Saad DF,Milas Z.Laparoscopic adrenalectomy for neuroblastoma in children: a report of 6 cases..J Pediatr Surg2005;40:1948-50

[21] Santana VM,McGregor LM.Disease control intervals in high-risk neuroblastoma..Cancer2008;112:2796-801

[22] Simon T,Borkhardt A,De Carolis B.Treatment and outcomes of patients with relapsed, high-risk neuroblastoma: results of German trials..Pediatr Blood Cancer2011;56:578-83

[23] Molenaar JJ,Koster J,van Noesel CJ.Cyclin D1 and CDK4 activity contribute to the undifferentiated phenotype in neuroblastoma..Cancer Res2008;68:2599-609

[24] Barbieri E,Capasso M,Hsu DM.Histone chaperone CHAF1A inhibits differentiation and promotes aggressive neuroblastoma..Cancer Res2014;74:765-74

[25] Schleiermacher G,Delattre O.Recent insights into the biology of neuroblastoma..Int J Cancer2014;135:2249-61

[26] Lee RC,Ambros V.The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14..Cell1993;75:843-54

[27] Lagos-Quintana M,Yalcin A,Lendeckel W.Identification of tissue-specific microRNAs from mouse..Curr Biol2002;12:735-9

[28] Wienholds E,Miska E,Berezikov E.MicroRNA expression in zebrafish embryonic development..Science2005;309:310-1

[29] Carthew RW.Origins and mechanisms of miRNAs and siRNAs..Cell2009;136:642-55 PMCID:PMC2675692

[30] Hayashita Y,Tatematsu Y,Yanagisawa K.A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation..Cancer Res2005;65:9628-32

[31] O’Donnell KA,Zeller KI,Mendell JT.c-Myc-regulated microRNAs modulate E2F1 expression..Nature2005;435:839-43

[32] Chen JF,Thomson JM,Callis TE.The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation..Nat Genet2006;38:228-33 PMCID:PMC2538576

[33] Dews M,Yu D,Sevignani C.Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster..Nat Genet2006;38:1060-5 PMCID:PMC2669546

[34] Hossain A,Saunders GF.Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA..Mol Cell Biol2006;26:8191-201 PMCID:PMC1636750

[35] Volinia S,Liu CG,Cimmino A.A microRNA expression signature of human solid tumors defines cancer gene targets..Proc Natl Acad Sci U S A2006;103:2257-61 PMCID:PMC1413718

[36] Sylvestre Y,Querido E,Bourdeau V.An E2F/miR-20a autoregulatory feedback loop..J Biol Chem2007;282:2135-43

[37] Venturini L,Castoldi M,Hochhaus A.Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells..Blood2007;109:4399-405

[38] Murray MJ,Raby KL,Gillis AJ.A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours..Br J Cancer2016;114:151-62 PMCID:PMC4815809

[39] Macfarlane LA.MicroRNA: biogenesis, function and role in cancer..Curr Genomics2010;11:537-61 PMCID:PMC3048316

[40] Sarkar J,Turaka P,Ramchandran R.MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell proliferation and migration..Am J Physiol Lung Cell Mol Physiol2010;299:L861-71 PMCID:PMC3006273

[41] Frankel LB.MicroRNA regulation of autophagy..Carcinogenesis2012;33:2018-25

[42] Xia H.MicroRNAs involved in regulating epithelial-mesenchymal transition and cancer stem cells as molecular targets for cancer therapeutics..Cancer Gene Ther2012;19:723-30

[43] Brueckner B,Kuner R,Musch T.The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function..Cancer Res2007;67:1419-23

[44] Scott GK,Bhaumik D,Sullivan CS.Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b..J Biol Chem2007;282:1479-86

[45] Calin GA,Sevignani C,Felli N.MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias..Proc Natl Acad Sci U S A2004;101:11755-60 PMCID:PMC511048

[46] Mattie MD,Bowers J,Wong L.Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies..Mol Cancer2006;5:24 PMCID:PMC1563474

[47] Lee EJ,Jiang J,Lerner MR.Expression profiling identifies microRNA signature in pancreatic cancer..Int J Cancer2007;120:1046-54 PMCID:PMC2680248

[48] Johnson SM,Shingara J,Jarvis R.RAS is regulated by the let-7 microRNA family..Cell2005;120:635-47

[49] Calin GA,Shimizu M,Zupo S.Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia..Proc Natl Acad Sci U S A2002;99:15524-9 PMCID:PMC137750

[50] Place RF,Pookot D,Dahiya R.MicroRNA-373 induces expression of genes with complementary promoter sequences..Proc Natl Acad Sci U S A2008;105:1608-13 PMCID:PMC2234192

[51] Khraiwesh B,Seumel GI,Weigel D.Transcriptional control of gene expression by microRNAs..Cell2010;140:111-22

[52] Vasudevan S,Steitz JA.Switching from repression to activation: microRNAs can up-regulate translation..Science2007;318:1931-4

[53] Ward NJ,Higgins J,Munsterberg A.MicroRNAs associated with early neural crest development in Xenopus laevis..BMC Genomics2018;19:59 PMCID:PMC5774138

[54] Weiner AMJ.MicroRNAs and the neural crest: from induction to differentiation..Mech Dev2018;154:98-106

[55] Sheehy NT,White MP,Srivastava D.The neural crest-enriched microRNA miR-452 regulates epithelial-mesenchymal signaling in the first pharyngeal arch..Development2010;137:4307-16 PMCID:PMC2990216

[56] Beckers A,Carter DR,Althoff K.MYCN-targeting miRNAs are predominantly downregulated during MYCNdriven neuroblastoma tumor formation..Oncotarget2015;6:5204-16 PMCID:PMC4467143

[57] Ooi CY,Liu B,Beckers A.Network modeling of microRNA-mRNA interactions in neuroblastoma tumorigenesis identifies miR-204 as a direct inhibitor of MYCN..Cancer Res2018;78:3122-34

[58] Zhao Z,Hsiao TH,Kosti A.A high-content morphological screen identifies novel microRNAs that regulate neuroblastoma cell differentiation..Oncotarget2014;5:2499-512 PMCID:PMC4058022

[59] Zhao Z,Sung D,Kosti A.MicroRNA-449a functions as a tumor suppressor in neuroblastoma through inducing cell differentiation and cell cycle arrest..RNA Biol2015;12:538-54 PMCID:PMC4615578

[60] Zhao Z,Shelton SD,Li M.A combined gene expression and functional study reveals the crosstalk between N-Myc and differentiation-inducing microRNAs in neuroblastoma cells..Oncotarget2016;7:79372-87 PMCID:PMC5346721

[61] Zhao Z,Sousares M,Holland CL.MicroRNA-2110 functions as an onco-suppressor in neuroblastoma by directly targeting Tsukushi..PLoS One2018;13:e0208777 PMCID:PMC6294380

[62] Stallings RL.MicroRNA involvement in the pathogenesis of neuroblastoma: potential for microRNA mediated therapeutics..Curr Pharm Des2009;15:456-62 PMCID:PMC2945477

[63] Schulte JH,Schlierf S,Heukamp LC.MicroRNAs in the pathogenesis of neuroblastoma..Cancer Lett2009;274:10-5

[64] Brodeur GM.Neuroblastoma: biological insights into a clinical enigma..Nat Rev Cancer2003;3:203-16

[65] Tonini GP.Genetic and epigenetic alterations in neuroblastoma..Cancer Lett2003;197:69-73

[66] Chen Y.Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis..Cancer Res2007;67:976-83

[67] Buechner J.N-myc and noncoding RNAs in neuroblastoma..Mol Cancer Res2012;10:1243-53

[68] Bray I,Prenter S,Foley NH.Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival..PLoS One2009;4:e7850 PMCID:PMC2773120

[69] Das S,Buckley PG,Bray IM.Modulation of neuroblastoma disease pathogenesis by an extensive network of epigenetically regulated microRNAs..Oncogene2013;32:2927-36 PMCID:PMC3477279

[70] Romania P,Bracaglia G,Fruci D.Epigenetic deregulation of microRNAs in rhabdomyosarcoma and neuroblastoma and translational perspectives..Int J Mol Sci2012;13:16554-79 PMCID:PMC3546707

[71] Parodi F,Ragusa M,Maugeri M.Epigenetic dysregulation in neuroblastoma: a tale of miRNAs and DNA methylation..Biochim Biophys Acta2016;1859:1502-14

[72] He XY,Mou Q,Liu S.MicroRNA-221 enhances MYCN via targeting nemo-like kinase and functions as an oncogene related to poor prognosis in neuroblastoma..Clin Cancer Res2017;23:2905-18

[73] Zhao D,Li P,Xiao A.MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68..Mol Med Rep2015;12:5554-60

[74] Xiang X,Zhao X,Li D.miRNA-337-3p suppresses neuroblastoma progression by repressing the transcription of matrix metalloproteinase 14..Oncotarget2015;6:22452-66 PMCID:PMC4673175

[75] Xiang X,Qu H,Li D.miRNA-584-5p exerts tumor suppressive functions in human neuroblastoma through repressing transcription of matrix metalloproteinase 14..Biochim Biophys Acta2015;1852:1743-54

[76] Meng H,Zhang X,Shen R.MiR-449a regulates the cell migration and invasion of human non-small cell lung carcinoma by targeting ADAM10..Onco Targets Ther2019;12:3829-38 PMCID:PMC6529029

[77] Cheng J,Deng XS,Lv Z.MicroRNA-449a suppresses hepatocellular carcinoma cell growth via G1 phase arrest and the HGF/MET c-Met pathway..Hepatobiliary Pancreat Dis Int2018;17:336-44

[78] Li F,Bai L.MicroRNA-449a functions as a tumor suppressor in pancreatic cancer by the epigenetic regulation of ATDC expression..Biomed Pharmacother2018;103:782-9

[79] Xu B,Wang S.MiR-449a suppresses cell migration and invasion by targeting PLAGL2 in breast cancer..Pathol Res Pract2018;214:790-5

[80] Li Y,Shao L,Zheng C.Mir-449a, a potential diagnostic biomarker for WNT group of medulloblastoma..J Neurooncol2016;129:423-31

[81] Mao A,Wang Y,Zhou X.miR-449a enhances radiosensitivity through modulating pRb/E2F1 in prostate cancer cells..Tumour Biol2016;37:4831-40

[82] Silber J,Petritsch C,Maunakea AK.miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells..BMC Med2008;6:14 PMCID:PMC2443372

[83] Ko HY,Lee YS,Ali BA.Bioimaging of transcriptional activity of microRNA124a during neurogenesis..Biotechnol Lett2015;37:2333-40

[84] Choi KH,Lee WJ,Kim HH.Dual-strand tumor suppressor miR-193b-3p and -5p inhibit malignant phenotypes of lung cancer by suppressing their common targets..Biosci Rep2019;39:BSR20190634 PMCID:PMC6630026

[85] Hashemi ZS,Khalili S,Salimi F.Additive effect of metastamiR-193b and breast cancer metastasis suppressor 1 as an anti-metastatic strategy..Breast Cancer2019;26:215-28

[86] Bhayadia R,Haetscher N,Emmrich S.Endogenous tumor suppressor microRNA-193b: therapeutic and prognostic value in acute myeloid leukemia..J Clin Oncol2018;36:1007-16

[87] Mitra AK,Tiwari P,Watters KM.Microenvironment-induced downregulation of miR-193b drives ovarian cancer metastasis..Oncogene2015;34:5923-32 PMCID:PMC4580483

[88] Chen J,Lentz C,Pare GC.miR-193b regulates Mcl-1 in melanoma..Am J Pathol2011;179:2162-8 PMCID:PMC3204027

[89] Roth SA,Fuchs S,Mikkola I.MicroRNA-193b-3p represses neuroblastoma cell growth via downregulation of Cyclin D1, MCL-1 and MYCN..Oncotarget2018;9:18160-79 PMCID:PMC5915064

[90] Zhang H,Qi T,Yang C.MicroRNA-145 inhibits the growth, invasion, metastasis and angiogenesis of neuroblastoma cells through targeting hypoxia-inducible factor 2 alpha..Oncogene2014;33:387-97

[91] Ye D,Deng H,Zhou S.MicroRNA-145 inhibits growth of laryngeal squamous cell carcinoma by targeting the PI3K/Akt signaling pathway..Cancer Manag Res2019;11:3801-12 PMCID:PMC6500435

[92] Zhang XF,Chang ZX,Guo H.MicroRNA145 modulates migration and invasion of bladder cancer cells by targeting Ncadherin..Mol Med Rep2018;17:8450-6

[93] Lin Y,Wen Y,Chen QD.MiRNA-145 increases therapeutic sensibility to gemcitabine treatment of pancreatic adenocarcinoma cells..Oncotarget2016;7:70857-68 PMCID:PMC5342594

[94] Chen Y,Rao Q,Li L.Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status..Oncotarget2015;6:31203-15 PMCID:PMC4741598

[95] Noguchi S,Hoshino Y,Nakagawa T.Comparative study of anti-oncogenic microRNA-145 in canine and human malignant melanoma..J Vet Med Sci2012;74:1-8

[96] Chen Z,Guo Y,Pan H.miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc..J Exp Clin Cancer Res2010;29:151 PMCID:PMC2999592

[97] Wan X,Peng R,Chen Z.ROCK1, a novel target of miR-145, promotes glioma cell invasion..Mol Med Rep2014;9:1877-82

[98] Lee JJ,Iliopoulos D.MiR-27b targets PPARgamma to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells..Oncogene2012;31:3818-25 PMCID:PMC3290753

[99] Althoff K,Odersky A,Beckers A.miR-542-3p exerts tumor suppressive functions in neuroblastoma by downregulating Survivin..Int J Cancer2015;136:1308-20

[100] Wei JS,Durinck S,Cheuk AT.The MYCN oncogene is a direct target of miR-34a..Oncogene2008;27:5204-13 PMCID:PMC2562938

[101] Foley NH,Tivnan A,Murphy DM.MicroRNA-184 inhibits neuroblastoma cell survival through targeting the serine/threonine kinase AKT2..Mol Cancer2010;9:83 PMCID:PMC2864218

[102] Stallings RL,Bryan K,Bray I.Therapeutic targeting of miRNAs in neuroblastoma..Expert Opin Ther Targets2010;14:951-62

[103] Tivnan A,Buckley PG,Davidoff AM.MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma..BMC Cancer2011;11:33 PMCID:PMC3038978

[104] Chen Y,Tseng SH.Inhibition of cyclin-dependent kinase 1-induced cell death in neuroblastoma cells through the microRNA-34a-MYCN-survivin pathway..Surgery2013;153:4-16

[105] Terrile M,Vaughan L,Webber H.miRNA expression profiling of the murine TH-MYCN neuroblastoma model reveals similarities with human tumors and identifies novel candidate miRNAs..PLoS One2011;6:e28356 PMCID:PMC3229581

[106] Lynch J,Meehan M,Watters KM.MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF-beta signalling pathway..Carcinogenesis2012;33:976-85 PMCID:PMC3334516

[107] Zhang H,Li S,Mei H.MicroRNA-9 targets matrix metalloproteinase 14 to inhibit invasion, metastasis, and angiogenesis of neuroblastoma cells..Mol Cancer Ther2012;11:1454-66

[108] Chio CC,Cheng HA,Wang YH.MicroRNA-210 targets antiapoptotic Bcl-2 expression and mediates hypoxia-induced apoptosis of neuroblastoma cells..Arch Toxicol2013;87:459-68

[109] Li Y,Li J.MiR-181c modulates the proliferation, migration, and invasion of neuroblastoma cells by targeting Smad7..Acta Biochim Biophys Sin (Shanghai)2014;46:48-55

[110] Maugeri M,Barbagallo C,Di Mauro S.Altered expression of miRNAs and methylation of their promoters are correlated in neuroblastoma..Oncotarget2016;7:83330-41 PMCID:PMC5347773

[111] Lodrini M,Schroeder C,Schier MC.MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma..Nucleic Acids Res2013;41:6018-33 PMCID:PMC3695529

[112] Lodrini M,Schmidt V,Dreidax D.Minichromosome maintenance complex is a critical node in the miR-183 signaling network of MYCN-amplified neuroblastoma cells..J Proteome Res2016;15:2178-86

[113] Wang K,Zhang H,Winter C.Integrative genomics identifies LMO1 as a neuroblastoma oncogene..Nature2011;469:216-20 PMCID:PMC3320515

[114] Saeki N,Sugaya Y,Sasaki H.Indirect down-regulation of tumor-suppressive let-7 family microRNAs by LMO1 in neuroblastoma..Cancer Genomics Proteomics2018;15:413-20 PMCID:PMC6199578

[115] Powers JT,Pearson DS,Spina CS.Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma..Nature2016;535:246-51 PMCID:PMC4947006

[116] Soriano A,Boloix A,Paris-Coderch L.Functional high-throughput screening reveals miR-323a-5p and miR-342-5p as new tumor-suppressive microRNA for neuroblastoma..Cell Mol Life Sci2019;76:2231-43 PMCID:PMC6502783

[117] Beckers A,Carter DR,Herrmann C.MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma..Cancer Lett2015;366:123-32 PMCID:PMC4837470

[118] Chen X,Han L,Hao X.miR-338-3p suppresses neuroblastoma proliferation, invasion and migration through targeting PREX2a..FEBS Lett2013;587:3729-37

[119] Raghunath M,Bannerman P,Baker S.A novel kinase, AATYK induces and promotes neuronal differentiation in a human neuroblastoma (SH-SY5Y) cell line..Brain Res Mol Brain Res2000;77:151-62

[120] Rodriguez A,Ashurst JL.Identification of mammalian microRNA host genes and transcription units..Genome Res2004;14:1902-10 PMCID:PMC524413

[121] Wu T,Xie Z.MicroRNA-1247 inhibits cell proliferation by directly targeting ZNF346 in childhood neuroblastoma..Biol Res2018;51:13 PMCID:PMC5966945

[122] Li SH,Chen L.miR-146a induces apoptosis in neuroblastoma cells by targeting BCL11A..Med Hypotheses2018;117:21-7

[123] Feinberg-Gorenshtein G,Shichrur K,Luria D.MiR-192 directly binds and regulates Dicer1 expression in neuroblastoma..PLoS One2013;8:e78713 PMCID:PMC3815303

[124] Qu H,Pu J,Xiang X.miRNA-558 promotes tumorigenesis and aggressiveness of neuroblastoma cells through activating the transcription of heparanase..Hum Mol Genet2015;24:2539-51

[125] Qu H,Song H,Li D.MicroRNA-558 facilitates the expression of hypoxia-inducible factor 2 alpha through binding to 5’-untranslated region in neuroblastoma..Oncotarget2016;7:40657-73 PMCID:PMC5130034

[126] Liu G,Hao D.MicroRNA451 inhibits neuroblastoma proliferation, invasion and migration by targeting macrophage migration inhibitory factor..Mol Med Rep2016;13:2253-60

[127] Li Z,Xie Q,Xie J.miR-1303 promotes the proliferation of neuroblastoma cell SH-SY5Y by targeting GSK3beta and SFRP1..Biomed Pharmacother2016;83:508-13

[128] Hsu DM,Benham A,Trahan DN.G-CSF receptor positive neuroblastoma subpopulations are enriched in chemotherapy-resistant or relapsed tumors and are highly tumorigenic..Cancer Res2013;73:4134-46 PMCID:PMC4298227

[129] Liu X,Liao W,Cai M.MiR-181a/b induce the growth, invasion, and metastasis of neuroblastoma cells through targeting ABI1..Mol Carcinog2018;57:1237-50

[130] Swarbrick A,Shaw A,Phua Y.miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma..Nat Med2010;16:1134-40 PMCID:PMC3019350

[131] De Preter K,Vermeulen J,Naranjo A.miRNA expression profiling enables risk stratification in archived and fresh neuroblastoma tumor samples..Clin Cancer Res2011;17:7684-92 PMCID:PMC4008338

[132] Chen Y,Fang Y.Micro-RNA-21 regulates the sensitivity to cisplatin in human neuroblastoma cells..J Pediatr Surg2012;47:1797-805

[133] Buechner J,Haug BH,Flaegstad T.Inhibition of mir-21, which is up-regulated during MYCN knockdown-mediated differentiation, does not prevent differentiation of neuroblastoma cells..Differentiation2011;81:25-34

[134] Fontana L,Albini S,Giovinazzi S.Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM..PLoS One2008;3:e2236 PMCID:PMC2375057

[135] Buhagiar A.Chemoresistance, cancer stem cells, and miRNA influences: the case for neuroblastoma..Anal Cell Pathol (Amst)2015;2015:150634 PMCID:PMC4516851

[136] Ribeiro D,Westermark UK,Dzieran J.Regulation of nuclear hormone receptors by MYCN-driven miRNAs impacts neural differentiation and survival in neuroblastoma patients..Cell Rep2016;16:979-93

[137] Takwi AA,Wu J,Cinatl J.miR-137 regulates the constitutive androstane receptor and modulates doxorubicin sensitivity in parental and doxorubicin-resistant neuroblastoma cells..Oncogene2014;33:3717-29 PMCID:PMC3922897

[138] Sun F,Liu Q,Zhu J.Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest..FEBS Lett2008;582:1564-8

[139] Tivnan A,Gubala V,Williams DE.Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a using anti-disialoganglioside GD2 coated nanoparticles..PLoS One2012;7:e38129 PMCID:PMC3360657

[140] Marengo B,Miele M,Ottaggio L.Etoposide-resistance in a neuroblastoma model cell line is associated with 13q14.3 mono-allelic deletion and miRNA-15a/16-1 down-regulation..Sci Rep2018;8:13762 PMCID:PMC6137223

[141] Ryan J,Fay J,Meehan M.MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome..Br J Cancer2012;107:967-76 PMCID:PMC3464768

[142] Arevalo JC.Neurotrophin signaling: many exciting surprises!.Cell Mol Life Sci2006;63:1523-37

[143] Sun YX,Wang PY,Xie SY.Cisplatin regulates SH-SY5Y cell growth through downregulation of BDNF via miR-16..Oncol Rep2013;30:2343-9

[144] Creevey L,Harvey H,Meehan M.MicroRNA-497 increases apoptosis in MYCN amplified neuroblastoma cells by targeting the key cell cycle regulator WEE1..Mol Cancer2013;12:23 PMCID:PMC3626575

[145] Bhavsar SP,Flaegstad T.Hsa-miR-376c-3p targets Cyclin D1 and induces G1-cell cycle arrest in neuroblastoma cells..Oncol Lett2018;16:6786-94 PMCID:PMC6202480

[146] Ayers D,Van Maerken T.Identification of miRNAs contributing to neuroblastoma chemoresistance..Comput Struct Biotechnol J2015;13:307-19 PMCID:PMC4427660

[147] Zhi F,Wang Q,Deng D.MicroRNAs in neuroblastoma: small-sized players with a large impact..Neurochem Res2014;39:613-23

[148] Tivnan A,Tracey L,Stallings RL.MicroRNA-184-mediated inhibition of tumour growth in an orthotopic murine model of neuroblastoma..Anticancer Res2010;30:4391-5 PMCID:PMC5030819

[149] Chakrabarti M,Banik NL.Alterations in expression of specific microRNAs by combination of 4-HPR and EGCG inhibited growth of human malignant neuroblastoma cells..Brain Res2012;1454:1-13 PMCID:PMC3335959

[150] Harvey H,Creevey L,Buckley PG.Modulation of chemotherapeutic drug resistance in neuroblastoma SK-N-AS cells by the neural apoptosis inhibitory protein and miR-520f..Int J Cancer2015;136:1579-88

[151] Challagundla KB,Neviani P,Murtadha M.Exosome-mediated transfer of microRNAs within the tumor microenvironment and neuroblastoma resistance to chemotherapy..J Natl Cancer Inst2015;107:djv135 PMCID:PMC4651042

[152] Haug BH,Utnes P,Lokke C.Exosome-like extracellular vesicles from MYCN-amplified neuroblastoma cells contain oncogenic miRNAs..Anticancer Res2015;35:2521-30

[153] Reynolds CP.Retinoid therapy of childhood cancer..Hematol Oncol Clin North Am2001;15:867-910

[154] Thiele CJ,Israel MA.Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma..Nature1985;313:404-6

[155] Truckenmiller ME,Cheadle C,Donovan DM.Gene expression profile in early stage of retinoic acid-induced differentiation of human SH-SY5Y neuroblastoma cells..Restor Neurol Neurosci2001;18:67-80

[156] Laneve P,Gioia U,Ferretti E.The interplay between microRNAs and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells..Proc Natl Acad Sci U S A2007;104:7957-62 PMCID:PMC1876554

[157] Meseguer S,Escamilla JM,Barettino D.MicroRNAs-10a and -10b contribute to retinoic acid-induced differentiation of neuroblastoma cells and target the alternative splicing regulatory factor SFRS1 (SF2/ASF)..J Biol Chem2011;286:4150-64 PMCID:PMC3039334

[158] Evangelisti C,Massimi I,Giannini G.MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness..FASEB J2009;23:4276-87

[159] Guidi M,Kagerbauer B,Estivill X.Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells..BMC Mol Biol2010;11:95 PMCID:PMC3019150

[160] Roth SA,Fiskaa T,Bhavsar S.Next generation sequencing of microRNAs from isogenic neuroblastoma cell lines isolated before and after treatment..Cancer Lett2016;372:128-36

[161] Nallasamy P,Verma SS,Gorantla S.PD-L1, inflammation, non-coding RNAs, and neuroblastoma: immuno-oncology perspective..Semin Cancer Biol2018;52:53-65 PMCID:PMC5972043

[162] Verissimo CS,Fitzsimons CP.Neuroblastoma therapy: what is in the pipeline?.Endocr Relat Cancer2011;18:R213-31

[163] Ramachandran M,Dyczynski M,Zhang L.Safe and effective treatment of experimental neuroblastoma and glioblastoma using systemically delivered triple microRNA-detargeted oncolytic semliki forest virus..Clin Cancer Res2017;23:1519-30

[164] Du X,Xu F,Liu Z.Enterovirus 71 induces apoptosis of SHSY5Y human neuroblastoma cells through stimulation of endogenous microRNA let-7b expression..Mol Med Rep2015;12:953-9 PMCID:PMC4438926

[165] Mundalil Vasu M,Takahashi T,Iwata K.Fluoxetine increases the expression of miR-572 and miR-663a in human neuroblastoma cell lines..PLoS One2016;11:e0164425 PMCID:PMC5055328

[166] Sousares M,Weigum S.MicroRNAs in neuroblastoma differentiation and differentiation therapy..Adv Mod Oncol Res2017;3:213-22

[167] Curtin C,Conlon R,Gallagher C.A physiologically relevant 3D collagen-based scaffold-neuroblastoma cell system exhibits chemosensitivity similar to orthotopic xenograft models..Acta Biomater2018;70:84-97

[168] Wang X,Xu X,Li Q.miR-129 inhibits tumor growth and potentiates chemosensitivity of neuroblastoma by targeting MYO10..Biomed Pharmacother2018;103:1312-8

[169] Ramaiah MJ,Lavanya A,Haritha V.Novel anthranilamide-pyrazolo[1,5-a]pyrimidine conjugates modulate the expression of p53-MYCN associated micro RNAs in neuroblastoma cells and cause cell cycle arrest and apoptosis..Bioorg Med Chem Lett2013;23:5699-706

[170] Ren X,Zhang X,Tang L.Quantitative nuclear proteomics identifies that miR-137-mediated EZH2 reduction regulates resveratrol-induced apoptosis of neuroblastoma cells..Mol Cell Proteomics2015;14:316-28 PMCID:PMC4350028

[171] Vanhauwaert S,De Brouwer S,Durinck K.In silico discovery of a FOXM1 driven embryonal signaling pathway in therapy resistant neuroblastoma tumors..Sci Rep2018;8:17468 PMCID:PMC6269481

[172] Gonzalez-Nunez V,Rodriguez RE.Morphine modulates cell proliferation through mir133b &mir128 in the neuroblastoma SH-SY5Y cell line..Biochim Biophys Acta2014;1842:566-72

[173] Afanasyeva EA,Glatting KH.New miRNAs cloned from neuroblastoma..BMC Genomics2008;9:52 PMCID:PMC2254388