EXPRESSION OF GENES INVOLVED IN P53 PATHWAY REGULATION IN NEUROBLASTOMA: A SHORT REVIEW
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-4.18960Keywords:
gene expression, miRNA, neuroblastoma, p53 pathwayAbstract
The search for new prognostic and stratification genetic and epigenetic markers in neuroblastoma is an urgent problem in pediatric oncology. The review summarizes recent progress in studying the expression of genes involved in p53 pathway regulation in neuroblastoma. Several markers associated with recurrence risk and poor outcome are considered. Among them are MYCN amplification, high MDM2 and GSTP1 expression and homozygous mutant allele variant of GSTP1 gene A313G polymorphism. Prognostic criteria for neuroblastoma based on the analysis of miR-34a, miR-137, miR-380-5p, and miR-885-5p expression involved in regulating p53-mediated pathway are also considered. The authors’ research data on the role of the above markers in regulation of this pathway in neuroblastoma are presented. The study of alterations in expression of microRNAs and genes involved in p53 pathway regulation will not only expand our understanding of the mechanisms of neuroblastoma pathogenesis but could substantiate new approaches for delineating risk groups and risk stratification of neuroblastoma patients as well as treatment optimization based on the genetic characteristics of the tumor.
References
Maris JM, Hogarty MD, Bagatell R, et al. Neuroblastoma. Lancet 2007; 369: 2106–20. doi: https://doi.org/10.1016/S0140-6736(07)60983-0
Huang M, Weiss WA. Neuroblastoma and mycn. Cold Spring Harb Perspect Med 2013; 3: a015669. doi: https://doi.org/10.1101/cshperspect.a015669
Bagatell R, Beck-Popovic M, London WB, et al. Significance of mycn amplification in international neuroblastoma staging system stage 1 and 2 neuroblastoma: a report from the international neuroblastoma risk group database. J Clin Oncol 2009; 27: 365–70. doi: https://doi.org/10.1200/JCO.2008.17.9184
Canete A, Gerrard M., Rubie H, et al. Poor survival for infants with mycn-amprified metastatic neuroblastoma despite intensified treatment: the international society of paediatric oncology european neuroblastoma experience. J Clin Oncol 2009; 27: 1014–9. doi: https://doi.org/10.1200/JCO.2007.14.5839.
Bai L, Zhu W. P53 : structure, function and therapeutic applications. J Cancer Mol 2006; 2: 141–53. doi: 10.29685/JCM.200608.0002
Tweddle DA, Pearson AD, Haber M, et al. The p53 pathway and its inactivation in neuroblastoma. Cancer Lett 2003; 197: 93–8. doi: https://doi.org/10.1016/s0304-3835(03)00088-0.
Barone G, Tweddle D, Shohet JM, et al. MDM2-p53 interaction in paediatric solid tumours: preclinical rationale, biomarkers and resistance. Current Drug Targets 2014; 15: 114–23. PMID: 24387312.
Chen L, Iraci N, Gherardi S, et al. P53 is a direct transcriptional target of mycn in neuroblastoma. Cancer Res 2010; 70: 1377–88. doi: https://doi.org/10.1158/0008-5472
Zhi F, Wang R, Wang Q, et al. MicroRNAs in neuroblastoma: small-sized players with a large impact. Neurochem Res 2014; 39: 613–23. doi: https://doi.org/10.1007/s11064-014-1247-9
Stallings RL. MicroRNA involvement in the pathogenesis of neuroblastoma: potential for microrna mediated therapeutics. Curr Pharm Des 2009; 15: 456–62. doi: https://doi.org/10.2174/138161209787315837
Mei H, Lin ZY, Tong QS. The roles of micrornas in neuroblastoma. World J Pediatr 2014; 10: 10–6. doi: https://doi.org/10.1007/s12519-014-0448-2
Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene 2007; 26: 5017–50. doi: https://doi.org/10.1038/sj.onc.1210293
Cole K, Attiyeh EF, Mosse YP, et al. A functional screen identifies mir-34a as a candidate neuroblastoma tumor suppressor gene. Mol Cancer Res 2008; 6: 735–42. doi: https://doi.org/10.1158/1541-7786
Swarbrick A, Woods SL, Shaw A, et al. MiR-380-5p represses p53 to control cellular survival and is associated with poor outcome in mycn-amplified neuroblastoma. Nat Med 2010; 16: 1134–40. doi: https://doi.org/10.1038/nm.2227
Afanasyeva E, Mestdagh P, Kumps C, et al. MicroRNA mir-885-5p targets cdk2 and mcm5, activates p53 and inhibits proliferation and survival. Cell Death Differ 2011; 18: 974–84. doi: 10.1038/cdd.2010.164
Althoff K, Beckers A, Odersky A, et al. MiR-137 functions as a tumor suppressor in neuroblastoma by downregulating kdm1a. Int J Cancer 2013; 133: 1064–73. doi: https://doi.org/10.1002/ijc.28091
Pugh TJ, Morozova O, Attiyeh EF, et al. The genetic landscape of high-risk neuroblastoma. Nat Genet 2013; 45: 279–84. doi: https://doi.org/10.1038/ng.2529
Raggi CC, Bagnoni ML, Tonini GP, et al. Real-time quantitative pcr for the measurement of mycn amplification in human neuroblastoma with the taqman detection system. Clin Chem 1999; 45: 1918–24.
Inomistova MV, Svergun NM, Khranovska NM, et al. Prognostic significance of mdm2 gene expression in childhood neuroblastoma. Exp Oncol 2015; 37: 111–5.
Pontén F, Jirström K, Uhlen M. The human protein atlas — a tool for pathology. J Pathol 2008; 216: 387–93. doi: https://doi.org/10.1002/path.2440
Uhlen M, Fagerberg L, Hallstrom BM, et al. Tissue-based map of the human proteome. Science 2015; 347: 1260419. doi: https://doi.org/10.1126/science.1260419
Uhlen M, Oksvold P, Fagerberg L, et al. Towards a knowledge-based human protein atlas. Nat Biotechnol 2010; 28: 1248–50. doi: https://doi.org/10.1038/nbt1210-1248
Mooneya MR, Kortac DJ, Bachmanna AS. Anti-tumor effect of sulfasalazine in neuroblastoma. Biochem Pharmacol 2019; 162: 237–49. https://doi.org/10.1016/j.bcp.2019.01.007
Carr-Wilkinson J. High frequency of p53/mdm2/p14arf pathway abnormalities in relapsed neuroblastoma. Clin Cancer Res 2010; 16: 1108–18. doi: https://doi.org/10.1158/1078-0432.CCR-09-1865
Maerken T, Vandesompele J, Rihani А, et al. Escape from p53-mediated tumor surveillance in neuroblastoma: switching off the p14(arf)-mdm2-p53 axis. Cell Death Differ 2009; 16: 1563–72. doi: https://doi.org/10.1038/cdd.2009.138
Xue C, Haber M, Flemming C, et al. P53 determines multidrug sensitivity of childhood neuroblastoma. Cancer Res 2007; 67: 10351–60. doi: https://doi.org/10.1158/0008-5472
Rayburn E, Zhang R, He J, et al. MDM2 and human malignancies: expression, clinical pathology, prognostic markers, and implications for chemotherapy. Curr Cancer Drug Targets 2005; 5: 27–41. doi: https://doi.org/10.2174/1568009053332636
Zhao Y, Yu H, Hu W. The regulation of mdm2 oncogene and its impact on human cancers. Acta Biochim Biophys Sin (Shanghai) 2014; 46: 180–9. doi: https://doi.org/10.1093/abbs/gmt147
Sciot R. MDM2 amplified sarcomas: A literature review. Diagnostics (Basel) 2021; 11: 496. doi: https://doi.org/10.3390/diagnostics11030496
Reifenberger G, Liu L, Ichimura K, et al. Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res 1993; 53: 2736–9.
Schmidt MK, Reincke S, Broeks A, et al. Do mdm2 snp309 and tp53 r72p interact in breast cancer susceptibility? a large pooled series from the breast cancer association consortium. Cancer Res 2007; 67: 9584–90. doi: https://doi.org/10.1158/0008-5472
Yu Q, Li Y, Mu K, et al. Amplification of mdmx and overexpression of mdm2 contribute to mammary carcinogenesis by substituting for p53 mutations. Diagn Pathol 2014; 9: 71. doi: https://doi.org/10.1186/1746-1596-9-71
Slack A, Lozano G, Shohet JM. MDM2 as MYCN transcriptional target: implications for neuroblastoma pathogenesis. Cancer Lett 2005; 228: 21–7. doi: https://doi.org/10.1016/j.canlet.2005.01.050.
Zhang H, Gu L, Li J, et al. MDM2 regulates MYCN mRNA stabilization and translation in human neuroblastoma cells. Oncogene 2012; 31: 1342–53. doi: https://doi.org/10.1038/onc.2011.343
Brooks CL, Gu W. New insights into p53 activation. Cell Res 2010; 20: 614–21. doi: https://doi.org/10.1038/cr.2010.53
Barbieri E, De Preter K, Capasso M, et al. A p53 drug response signature identifies prognostic genes in high-risk neuroblastoma. PLoS One 2013; 8: e79843. doi: https://doi.org/10.1371/journal.pone.0079843
Gumy-Pause F, Pardo B, Khoshbeen-Boudal M, et al. GSTP1 hypermethylation is associated with reduced protein expression, aggressive disease and prognosis in neuroblastoma. Genes Chromosomes Cancer 2012; 51: 174–85. doi: https://doi.org/10.1002/gcc.20941
Townsend DM, Tew KD. The role of glutathione-s-transferase in anti-cancer drug resistance. Oncogene 2003; 22: 7369-75. doi: 10.1038/sj.onc.1206940
Zhang BL, Sun T, Zhang BN, et al. Polymorphisms of gstp1 is associated with differences of chemotherapy response and toxicity in breast cancer. Chin Med J (Engl) 2011; 124: 199–204.
Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005; 45: 51–88. doi: https://doi.org/10.1146/annurev.pharmtox.45.120403.095857
Lo H-W, Stephenson L, Cao X, et al. Identification and functional characterization of the human glutathione s-transferase p1 gene as a novel transcriptional target of the p53 tumor suppressor gene. Mol Cancer Res 2008; 6: 843–50. doi: https://doi.org/10.1158/1541-7786
Rothenberg AB, Berdon WE, D’Angio GJ, et al. Neuroblastoma—remembering the three physicians who described it a century ago: James Homer Wright, William Pepper and Robert Hutchison. Pediatr Radiol 2009; 39: 155–60. doi: https://doi.org/10.1007/s00247-008-1062-z
Ben Salah G, Kallabi F, Maatoug S, et al. Polymorphisms of glutathione s-transferases m1, t1, p1 and a1 genes in the tunisian population: an intra and interethnic comparative approach. Gene 2012; 498: 317–22. doi: https://doi.org/10.1016/j.gene.2012.01.054
Fletcher JI, Gherardi S, Murray J, et al. N-Myc regulates expression of the detoxifying enzyme glutathione transferase GSTP1, a marker of poor outcome in neuroblastoma. Cancer Res 2012; 72: 845–53. doi: https://doi.org/10.1158/0008-5472.CAN-11-1885
Bellincampi L, Ballerini S, Bernardini S, et al. Glutathione transferase p1 polymorphism in neuroblastoma studied by endonuclease restriction mapping. Clin Chem Lab Med 2001; 39: 830–5. doi: https://doi.org/10.1515/CCLM.2001.138
Lanciotti M, Coco S, Di Michele P, et al. Glutathione s-transferase polymorphisms and susceptibility to neuroblastoma. Pharmacogenet Genomics 2005; 15: 423-6. doi: https://doi.org/10.1097/01213011-200506000-00008
Inomistova M, Khranovskaya NM, Skachkova OV, et al. GSTP1 gene expression and a313g polymorphism can affect neuroblastoma outcome. Pediatric Blood & Cancer 2017; 64: S230. https://doi.org/10.1002/pbc.26772
Hamilton M, Rajapakshe K, Hartig SM, et al. Identification of a pan-cancer oncogenic microrna superfamily anchored by a central core seed motif. Nat Commun 2013; 4: 2730. doi: https://doi.org/10.1038/ncomms3730
He L, He X, Lim LP, et al. A microrna component of the p53 tumour suppressor network. Nature 2007; 447: 1130–4. doi: https://doi.org/10.1038/nature05939
Hébert SS, De Strooper B. Molecular biology. miRNAs in neurodegeneration. Science 2007; 317: 1179–80. doi: https://doi.org/10.1126/science.1148530
Schulte JH, Schowe B, Mestdagh P, et al. Accurate prediction of neuroblastoma outcome based on miRNA expression profiles. Int J Cancer 2010; 127: 2374–85. doi: https://doi.org/10.1002/ijc.25436
Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annu Rev Med 2009; 60: 167–79. doi: https://doi.org/10.1146/annurev. med.59.053006.104707
Lodygin D, Tarasov V, Epanchintsev A, et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle 2008; 7: 2591–600. doi: https://doi.org/10.4161/cc.7.16.6533.
De Antonellis P, Carotenuto M, Vandenbussche J, et al. Early targets of mir-34a in neuroblastoma. Mol Cell Proteomics 2014; 13: 2114–31. doi: https://doi.org/10.1074/mcp.M113.035808
Inomistova MV, Khranovska NM, Skachkova OV, et al. MicroRNA mir-34 family expression and clinical outcome of neuroblastoma. Studia Biol 2016; 10: 5–14.
Smrt RD, Szulwach KE, Pfeiffer RL, et al. MicroRNA mir-137 regulates neuronal maturation by targeting ubiquitin ligase mind bomb-1. Stem Cells 2010; 28: 1060–70. doi: https://doi.org/10.1002/stem.431
Shi Y, Zhao X, Hsieh J, et al. MicroRNA regulation of neural stem cells and neurogenesis. J Neurosci 2010; 30: 14931–96. doi: https://doi.org/10.1523/JNEUROSCI.4280-10.2010
Althoff K, Beckers A, Odersky A, et al. MiR-137 functions as a tumor suppressor in neuroblastoma by downregulating KDM1a. Int J Cancer 2013; 133: 1064–73. doi: https://doi.org/10.1002/ijc.28091
Neault M, Mallette FA, Richard S. MiR-137 modulates a tumor suppressor network-inducing senescence in pancreatic cancer cells. Cell Rep 2016; 14: 1966–78. doi: https://doi.org/10.1016/j.celrep.2016.01.068
Inomistova MV, Khranovska NM, Skachkova OV, et al. MiR-137 expression in neuroblastoma: a role in clinical course and outcome. Biopol Cell 2016; 32: 222–8. doi: https://doi.org/10.7124/bc.000924
Inomistova MV, Khranovska NM, Skachkova OV, et al. Alteration of mir-380-5p exspression in neuroblastoma. Visnyk problem biologii’ i medycyny 2016; 3: 162–6.
Swarbrick A, Woods SL, Shaw A. Mir-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN amplified neuroblastoma. Nat Med 2010; 16: 1134–40. doi: https://doi.org/10.1038/nm.2227
Gui J, Tian Y, Wen X, et al. Serum microrna characterization identifies mir-885-5p as a potential marker for detecting liver pathologies. Clin Sci (Lond) 2011; 120: 183–93. doi: https://doi.org/10.1042/CS20100297
Inomistova M, Khranovska N, Skachkova O, et al. Significance of mir-885-5p in neuroblastoma outcome. Biol Stud 2015; 9: 23–30. doi: https://doi.org/10.30970/sbi.0903.450
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
