MicroRNA expression in pediatric intracranial ependymomas and their potential value for tumor grading

Cipro,Šimon; Belhajová,Marie; Eckschlager,Tomáš; Zámečník,Josef

doi:10.3892/ol.2018.9685

MicroRNA expression in pediatric intracranial ependymomas and their potential value for tumor grading

Authors:
- Šimon Cipro
- Marie Belhajová
- Tomáš Eckschlager
- Josef Zámečník
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Affiliations: Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University and University Hospital Motol, 150 06 Prague 5, Czech Republic, Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, 150 06 Prague 5, Czech Republic
Published online on: November 12, 2018 https://doi.org/10.3892/ol.2018.9685
Pages: 1379-1383

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Abstract

Intracranial ependymoma represents one of the most common pediatric central nervous system malignancies, and exhibits a wide range of clinical behavior from relatively indolent lesions to highly malignant anaplastic ependymomas. Due to the heterogeneous nature of this disease there is lack of prognostic markers, which would reliably predict the outcome of patients. MicroRNAs (miRNAs) have emerged as important molecules in cancer biology during past decade; however, very little is known about their role in ependymomas. The aim of the present study was to evaluate expression of miRNAs in archived formalin‑fixed paraffin‑embedded (FFPE) samples of pediatric intracranial ependymomas. The expression of miRNAs were examined in 29 samples of ependymoma and we observed that miR‑135a‑3p, miR‑137, miR‑17‑5p, miR‑181d and let‑7d‑5p were upregulated. In addition, a significantly higher expression of miR‑203a was detected in Grade III tumors suggesting its possible use as a prognostic or diagnostic marker. The present study also demonstrated that storage of (FFPE) ependymoma samples for >20 years did not result in a deterioration of miRNAs. The present findings broaden the presently available knowledge regarding miRNA expression in ependymomas and provide further evidence for the employment of miRNA analysis as a supplementary method for the morphological assessment of ependymoma samples.

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1	Gupta A and Dwivedi T: A simplified overview of World Health Organization classification update of central nervous system tumors 2016. J Neurosci Rural Pract. 8:629–641. 2017. View Article : Google Scholar : PubMed/NCBI
2	PDQ Pediatric Treatment Editorial Board: Childhood ependymoma treatment (PDQ^®): Health professional version. 2002.
3	Zamecnik J, Snuderl M, Eckschlager T, Chanova M, Hladikova M, Tichy M and Kodet R: Pediatric intracranial ependymomas: Prognostic relevance of histological, immunohistochemical, and flow cytometric factors. Mod Pathol. 16:980–991. 2003. View Article : Google Scholar : PubMed/NCBI
4	Hübner JM, Kool M, Pfister SM and Pajtler KW: Epidemiology, molecular classification and WHO grading of ependymoma. J Neurosurg Sci. 62:46–50. 2018.PubMed/NCBI
5	Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, Wani K, Tatevossian R, Punchihewa C, Johann P, et al: Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell. 27:728–743. 2015. View Article : Google Scholar : PubMed/NCBI
6	Pajtler KW, Mack SC, Ramaswamy V, Smith CA, Witt H, Smith A, Hansford JR, von Hoff K, Wright KD, Hwang E, et al: The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol. 133:5–12. 2017. View Article : Google Scholar : PubMed/NCBI
7	Tihan T, Zhou T, Holmes E, Burger PC, Ozuysal S and Rushing EJ: The prognostic value of histological grading of posterior fossa ependymomas in children: A Children's Oncology Group study and a review of prognostic factors. Mod Pathol. 21:165–177. 2008. View Article : Google Scholar : PubMed/NCBI
8	Hayes J, Peruzzi PP and Lawler S: MicroRNAs in cancer: Biomarkers, functions and therapy. Trends Mol Med. 20:460–469. 2014. View Article : Google Scholar : PubMed/NCBI
9	Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, et al: Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet. 37:766–770. 2005. View Article : Google Scholar : PubMed/NCBI
10	Vannini I, Fanini F and Fabbri M: Emerging roles of microRNAs in cancer. Curr Opin Genet Dev. 48:128–133. 2018. View Article : Google Scholar : PubMed/NCBI
11	Filipowicz W, Bhattacharyya SN and Sonenberg N: Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat Rev Genet. 9:102–114. 2008. View Article : Google Scholar : PubMed/NCBI
12	Zakrzewska M, Fendler W, Zakrzewski K, Sikorska B, Grajkowska W, Dembowska-Bagińska B, Filipek I, Stefańczyk Ł and Liberski PP: Altered MicroRNA expression is associated with tumor grade, molecular background and outcome in childhood infratentorial ependymoma. PLoS One. 11:e01584642016. View Article : Google Scholar : PubMed/NCBI
13	Costa FF, Bischof JM, Vanin EF, Lulla RR, Wang M, Sredni ST, Rajaram V, Mde Bonaldo F, Wang D, Goldman S, et al: Identification of microRNAs as potential prognostic markers in ependymoma. PLoS One. 6:e251142011. View Article : Google Scholar : PubMed/NCBI
14	Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, et al: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI
15	Wiggins JF, Ruffino L, Kelnar K, Omotola M, Patrawala L, Brown D and Bader AG: Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 70:5923–5930. 2010. View Article : Google Scholar : PubMed/NCBI
16	Misso G, Di Martino MT, De Rosa G, Farooqi AA, Lombardi A, Campani V, Zarone MR, Gullà A, Tagliaferri P, Tassone P and Caraglia M: Mir-34: A new weapon against cancer? Mol Ther Nucleic Acids. 3:e1942014. View Article : Google Scholar : PubMed/NCBI
17	Boyerinas B, Park SM, Hau A, Murmann AE and Peter ME: The role of let-7 in cell differentiation and cancer. Endocr Relat Cancer. 17:F19–F36. 2010. View Article : Google Scholar : PubMed/NCBI
18	Kolenda T, Przybyła W, Teresiak A, Mackiewicz A and Lamperska KM: The mystery of let-7d-a small RNA with great power. Contemp Oncol (Pozn). 18:293–301. 2014.PubMed/NCBI
19	Leeper H, Felicella MM and Walbert T: Recent advances in the classification and treatment of ependymomas. Curr Treat Options Oncol. 18:552017. View Article : Google Scholar : PubMed/NCBI
20	Yang CH, Wang Y, Sims M, Cai C, He P, Häcker H, Yue J, Cheng J, Boop FA and Pfeffer LM: MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon response pathway. Oncotarget. 8:112980–112991. 2017. View Article : Google Scholar : PubMed/NCBI
21	Liao H, Bai Y, Qiu S, Zheng L, Huang L, Liu T, Wang X, Liu Y, Xu N, Yan X and Guo H: MiR-203 downregulation is responsible for chemoresistance in human glioblastoma by promoting epithelial-mesenchymal transition via SNAI2. Oncotarget. 6:8914–8928. 2015. View Article : Google Scholar : PubMed/NCBI
22	Wang L, Sun H, Wang X, Hou N, Zhao L, Tong D, He K, Yang Y, Song T, Yang J and Huang C: EGR1 mediates miR-203a suppress the hepatocellular carcinoma cells progression by targeting HOXD3 through EGFR signaling pathway. Oncotarget. 7:45302–45316. 2016.PubMed/NCBI
23	Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, et al: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 299:425–436. 2008. View Article : Google Scholar : PubMed/NCBI
24	Bovell LC, Shanmugam C, Putcha BD, Katkoori VR, Zhang B, Bae S, Singh KP, Grizzle WE and Manne U: The prognostic value of microRNAs varies with patient race/ethnicity and stage of colorectal cancer. Clin Cancer Res. 19:3955–3965. 2013. View Article : Google Scholar : PubMed/NCBI
25	Greither T, Grochola LF, Udelnow A, Lautenschläger C, Würl P and Taubert H: Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer. 126:73–80. 2010. View Article : Google Scholar : PubMed/NCBI
26	Hu G, Lai P, Liu M, Xu L, Guo Z, Liu H, Li W, Wang G, Yao X, Zheng J and Xu Y: miR-203a regulates proliferation, migration, and apoptosis by targeting glycogen synthase kinase-3β in human renal cell carcinoma. Tumour Biol. 35:11443–11453. 2014. View Article : Google Scholar : PubMed/NCBI
27	Birks DK, Barton VN, Donson AM, Handler MH, Vibhakar R and Foreman NK: Survey of MicroRNA expression in pediatric brain tumors. Pediatr Blood Cancer. 56:211–216. 2011. View Article : Google Scholar : PubMed/NCBI
28	Margolin-Miller Y, Yanichkin N, Shichrur K, Toledano H, Ohali A, Tzaridis T, Michowitz S, Fichman-Horn S, Feinmesser M, Pfister SM, et al: Prognostic relevance of miR-124-3p and its target TP53INP1 in pediatric ependymoma. Genes Chromosomes Cancer. 56:639–650. 2017. View Article : Google Scholar : PubMed/NCBI
29	Liang Y, Yang W, Zhu Y and Yuan Y: Prognostic role of microRNA-203 in various carcinomas: Evidence from a meta-analysis involving 13 studies. Springerplus. 5:15382016. View Article : Google Scholar : PubMed/NCBI
30	Siebolts U, Varnholt H, Drebber U, Dienes HP, Wickenhauser C and Odenthal M: Tissues from routine pathology archives are suitable for microRNA analyses by quantitative PCR. J Clin Pathol. 62:84–88. 2009. View Article : Google Scholar : PubMed/NCBI