Biopolym. Cell. 2016; 32(3):222-228.
Biomedicine
MiR-137 expression in neuroblastoma: a role in clinical course and outcome.
1, 2Inomistova M. V., 1Khranovska N. M., 1Skachkova O. V., 1Klymniuk G. I., 2Demydov S. V., 1Svergun N. M.
  1. National Cancer Institute
    33/43, Lomonosova Str., Kyiv, Ukraine, 03022
  2. Educational and Scientific Center "Institute of Biology",
    Taras Shevchenko National University of Kyiv
    64/13, Volodymyrska Str., Kyiv, Ukraine, 01601

Abstract

Aim. To investigate association of the miR-137 expression in neuroblastoma patients with clinical and biological characteristics of the tumor, and the relationship with survival rates. Methods. qRT-PCR, FISH. Results. Analysis of 61 primary diagnosed neuroblastoma samples revealed a significantly lower expression of miR-137 in patients with the higher risk prognostic factors including the MYCN amplification, onset age, disease stage and overexpression of he p53 antagonist MDM2. Although miR-137 is not an independent risk factor, its higher expression was significantly associated with both improved event-free survival (5 year: 50.4 % vs 12.2 %) and overall survival (5 year: 46.9 % vs 19.1 %), indicating a potential tumor suppressor role in neuroblastoma. Conclusion. We identified miR-137 as a new microRNA of potential importance for the neuroblastoma tumor biology. We demonstrated that miR-137 expression can be used as a biomarker to stratify the neuroblastoma patients according to the clinical course.
Keywords: neuroblastoma, miR-137 expression

References

[1] Schulte JH, Schowe B, Mestdagh P, Kaderali L, Kalaghatgi P, Schlierf S, Vermeulen J, Brockmeyer B, Pajtler K, Thor T, de Preter K, Speleman F, Morik K, Eggert A, Vandesompele J, Schramm A. Accurate prediction of neuroblastoma outcome based on miRNA expression profiles. Int J Cancer. 2010;127(10):2374-85.
[2] Maris JM, Hogarty MD, Bagatell R, Cohn SL. Neuroblastoma. Lancet. 2007;369(9579):2106-20.
[3] Brodeur GM, Nakagawara A. Molecular basis of clinical heterogeneity in neuroblastoma. Am J Pediatr Hematol Oncol. 1992;14(2):111-6.
[4] Maris JM. The biologic basis for neuroblastoma heterogeneity and risk stratification. Curr Opin Pediatr. 2005;17(1):7-13.
[5] Garzon R, Calin GA, Croce CM. MicroRNAs in Cancer. Annu Rev Med. 2009;60:167-79.
[6] Shi Y, Zhao X, Hsieh J, Wichterle H, Impey S, Banerjee S, Neveu P, Kosik KS. MicroRNA regulation of neural stem cells and neurogenesis. J Neurosci. 2010;30(45):14931-6.
[7] Smrt RD, Szulwach KE, Pfeiffer RL, Li X, Guo W, Pathania M, Teng ZQ, Luo Y, Peng J, Bordey A, Jin P, Zhao X. MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase mind bomb-1. Stem Cells. 2010;28(6):1060-70.
[8] Suzuki H, Takatsuka S, Akashi H, Yamamoto E, Nojima M, Maruyama R, Kai M, Yamano HO, Sasaki Y, Tokino T, Shinomura Y, Imai K, Toyota M. Genome-wide profiling of chromatin signatures reveals epigenetic regulation of MicroRNA genes in colorectal cancer. Cancer Res. 2011;71(17):5646-58.
[9] Althoff K, Beckers A, Odersky A, Mestdagh P, Köster J, Bray IM, Bryan K, Vandesompele J, Speleman F, Stallings RL, Schramm A, Eggert A, Sprüssel A, Schulte JH. MiR-137 functions as a tumor suppressor in neuroblastoma by downregulating KDM1A. Int J Cancer. 2013;133(5):1064-73.
[10] Magenta A, Rossini A, Fasanaro P, Pompilio G, Capogrossi MC MicroRNAs in Cardiac Regeneration, In: Ed Sen CK, MicroRNA in Regenerative Medicine. Elsevier Inc 2015; 917-42.
[11] Lee JM, Cho KW, Kim EJ, Tang Q, Kim KS, Tickle C, Jung HS. A contrasting function for miR-137 in embryonic mammogenesis and adult breast carcinogenesis. Oncotarget. 2015;6(26):22048-59.
[12] Neault M, Mallette FA, Richard S. miR-137 Modulates a Tumor Suppressor Network-Inducing Senescence in Pancreatic Cancer Cells. Cell Rep. 2016;14(8):1966-78.
[13] Carr-Wilkinson J, O'Toole K, Wood KM, Challen CC, Baker AG, Board JR, Evans L, Cole M, Cheung NK, Boos J, Köhler G, Leuschner I, Pearson AD, Lunec J, Tweddle DA. High Frequency of p53/MDM2/p14ARF Pathway Abnormalities in Relapsed Neuroblastoma. Clin Cancer Res. 2010;16(4):1108-18.
[14] Slack A, Lozano G, Shohet JM. MDM2 as MYCN transcriptional target: implications for neuroblastoma pathogenesis. Cancer Lett. 2005;228(1-2):21-7.
[15] Chen L, Iraci N, Gherardi S, Gamble LD, Wood KM, Perini G, Lunec J, Tweddle DA. p53 is a direct transcriptional target of MYCN in neuroblastoma. Cancer Res. 2010;70(4):1377-88.
[16] Huang M, Weiss WA. Neuroblastoma and MYCN. Cold Spring Harb Perspect Med. 2013;3(10):a014415.
[17] Beckers A, Ongenaert M, Decock A, Kumps C, Pattyn F, Neuroblastoma Research Consortium (NRC), Mestdagh P, Schulte J, Speleman F, De Preter K. MiR-137 is epigenetically silenced in MYCN amplified neuroblastomas and targets the polycomb repressive complex 2 (PRC2) component EZH2. Advances in Neuroblastoma Research (Abstracts). Toronto. 2012:id 4432060
[18] Inomistova MV, Svergun NM, Khranovska NM, Skachkova OV, Gorbach OI, Klymnyuk GI. Prognostic significance of MDM2 gene expression in childhood neuroblastoma. Exp Oncol. 2015;37(2):111-5.
[19] Evans AE, D'Angio GJ. Age at diagnosis and prognosis in children with neuroblastoma. J Clin Oncol. 2005;23(27):6443-4.
[20] Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, Faldum A, Hero B, Iehara T, Machin D, Mosseri V, Simon T, Garaventa A, Castel V, Matthay KK; INRG Task Force. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol. 2009;27(2):289-97.