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Pleiotropic effects of miR-183~96~182 converge to regulate cell survival, proliferation and migration in medulloblastoma

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Abstract

Medulloblastomas are the most common malignant brain tumors in children. Several large-scale genomic studies have detailed their heterogeneity, defining multiple subtypes with unique molecular profiles and clinical behavior. Increased expression of the miR-183~96~182 cluster of microRNAs has been noted in several subgroups, including the most clinically aggressive subgroup associated with genetic amplification of MYC. To understand the contribution of miR-183~96~182 to the pathogenesis of this aggressive subtype of medulloblastoma, we analyzed global gene expression and proteomic changes that occur upon modulation of miRNAs in this cluster individually and as a group in MYC-amplified medulloblastoma cells. Knockdown of the full miR-183~96~182 cluster results in enrichment of genes associated with apoptosis and dysregulation of the PI3K/AKT/mTOR signaling axis. Conversely, there is a relative enrichment of pathways associated with migration, metastasis and epithelial to mesenchymal transition, as well as pathways associated with dysfunction of DNA repair in cells with preserved miR-183 cluster expression. Immunocytochemistry and FACS analysis confirm induction of apoptosis upon knockdown of the miR-183 cluster. Importantly, cell-based migration and invasion assays verify the positive regulation of cell motility/migration by the miR-183 cluster, which is largely mediated by miR-182. We show that the effects on cell migration induced by the miR-183 cluster are coupled to the PI3K/AKT/mTOR pathway through differential regulation of AKT1 and AKT2 isoforms. Furthermore, we show that rapamycin inhibits cell motility/migration in medulloblastoma cells and phenocopies miR-183 cluster knockdown. Thus, the miR-183 cluster regulates multiple biological programs that converge to support the maintenance and metastatic potential of medulloblastoma.

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References

  1. Abraham D, Jackson N, Gundara JS, Zhao J, Gill AJ, Delbridge L, Robinson BG, Sidhu SB (2011) MicroRNA profiling of sporadic and hereditary medullary thyroid cancer identifies predictors of nodal metastasis, prognosis, and potential therapeutic targets. Clin Cancer Res 17(14):4772–4781

    Google Scholar 

  2. Agiostratidou G, Hulit J, Phillips GR, Hazan RB (2007) Differential cadherin expression: potential markers for epithelial to mesenchymal transformation during tumor progression. J Mammary Gland Biol Neoplasia 12(2–3):127–133

    Article  PubMed  Google Scholar 

  3. Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, Schinzel AC, Sandy P, Meylan E, Scholl C, Frohling S, Chan EM, Sos ML, Michel K, Mermel C, Silver SJ, Weir BA, Reiling JH, Sheng Q, Gupta PB, Wadlow RC, Le H, Hoersch S, Wittner BS, Ramaswamy S, Livingston DM, Sabatini DM, Meyerson M, Thomas RK, Lander ES, Mesirov JP, Root DE, Gilliland DG, Jacks T, Hahn WC (2009) Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462(7269):108–112

    Article  PubMed  CAS  Google Scholar 

  4. Brunet JP, Tamayo P, Golub TR, Mesirov JP (2004) Metagenes and molecular pattern discovery using matrix factorization. Proc Natl Acad Sci USA 101(12):4164–4169

    Article  PubMed  CAS  Google Scholar 

  5. Bunt J, de Haas TG, Hasselt NE, Zwijnenburg DA, Koster J, Versteeg R, Kool M (2010) Regulation of cell cycle genes and induction of senescence by overexpression of OTX2 in medulloblastoma cell lines. Mol Cancer Res 8(10):1344–1357

    Google Scholar 

  6. Cannito S, Novo E, Compagnone A, Valfre di Bonzo L, Busletta C, Zamara E, Paternostro C, Povero D, Bandino A, Bozzo F, Cravanzola C, Bravoco V, Colombatto S, Parola M (2008) Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells. Carcinogenesis 29(12):2267–2278

    Article  PubMed  CAS  Google Scholar 

  7. CBTRUS (2009) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2004–2005. Central Brain Tumor Registry of the United States, Hinsdale, IL. http://www.cbtrus.org

  8. Chin YR, Toker A (2010) The actin-bundling protein palladin is an Akt1-specific substrate that regulates breast cancer cell migration. Mol Cell 38(3):333–344

    Google Scholar 

  9. Chin YR, Toker A (2010) Akt2 regulates expression of the actin-bundling protein palladin. FEBS Lett 584(23):4769–4774

    Google Scholar 

  10. Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, Berhoukim R, Amani V, Goumnerova L, Eberhart CG, Lau CC, Olson JM, Gilbertson RJ, Gajjar A, Delattre O, Kool M, Ligon K, Meyerson M, Mesirov JP, Pomeroy SL (2011) Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol 29(11):1424–1430

    Google Scholar 

  11. Copple BL (2010) Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia-inducible factor and transforming growth factor-beta-dependent mechanisms. Liver Int 30(5):669–682

    Google Scholar 

  12. Creighton CJ (2007) A gene transcription signature of the Akt/mTOR pathway in clinical breast tumors. Oncogene 26(32):4648–4655

    Article  PubMed  CAS  Google Scholar 

  13. de Iongh RU, Wederell E, Lovicu FJ, McAvoy JW (2005) Transforming growth factor-beta-induced epithelial-mesenchymal transition in the lens: a model for cataract formation. Cells Tissues Organs 179(1–2):43–55

    Article  PubMed  Google Scholar 

  14. Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4(9):721–726

    Article  PubMed  CAS  Google Scholar 

  15. Frame MC, Inman GJ (2008) NCAM is at the heart of reciprocal regulation of E-cadherin- and integrin-mediated adhesions via signaling modulation. Dev Cell 15(4):494–496

    Article  PubMed  CAS  Google Scholar 

  16. Guttilla IK, White BA (2009) Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. J Biol Chem 284(35):23204–23216

    Article  PubMed  CAS  Google Scholar 

  17. Han Y, Chen J, Zhao X, Liang C, Wang Y, Sun L, Jiang Z, Zhang Z, Yang R, Chen J, Li Z, Tang A, Li X, Ye J, Guan Z, Gui Y, Cai Z (2011) MicroRNA expression signatures of bladder cancer revealed by deep sequencing. PLoS One 6(3):e18286

    Google Scholar 

  18. Hannafon BN, Sebastiani P, de Las Morenas A, Lu J, Rosenberg CL (2011) Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer. Breast Cancer Res 13(2):R24

    Article  PubMed  CAS  Google Scholar 

  19. Harten SK, Shukla D, Barod R, Hergovich A, Balda MS, Matter K, Esteban MA, Maxwell PH (2009) Regulation of renal epithelial tight junctions by the von Hippel-Lindau tumor suppressor gene involves occludin and claudin 1 and is independent of E-cadherin. Mol Biol Cell 20(3):1089–1101

    Article  PubMed  CAS  Google Scholar 

  20. Horth P, Miller CA, Preckel T, Wenz C (2006) Efficient fractionation and improved protein identification by peptide OFFGEL electrophoresis. Mol Cell Proteomics 5(10):1968–1974

    Article  PubMed  Google Scholar 

  21. Hoshida Y, Brunet JP, Tamayo P, Golub TR, Mesirov JP (2007) Subclass mapping: identifying common subtypes in independent disease data sets. PLoS One 2(11):e1195

    Article  PubMed  Google Scholar 

  22. Irie HY, Pearline RV, Grueneberg D, Hsia M, Ravichandran P, Kothari N, Natesan S, Brugge JS (2005) Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition. J Cell Biol 171(6):1023–1034

    Article  PubMed  CAS  Google Scholar 

  23. Jiang J, Yang ES, Jiang G, Nowsheen S, Wang H, Wang T, Wang Y, Billheimer D, Chakravarthy AB, Brown M, Haffty B, Xia F (2011) p53-dependent BRCA1 nuclear export controls cellular susceptibility to DNA damage. Cancer Res 71:5546–5557

    Article  PubMed  CAS  Google Scholar 

  24. Kang YS, Li Y, Dai C, Kiss LP, Wu C, Liu Y (2010) Inhibition of integrin-linked kinase blocks podocyte epithelial-mesenchymal transition and ameliorates proteinuria. Kidney Int 78(4):363–373

    Google Scholar 

  25. Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J, Mrsic A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 3(8):e3088

    Article  PubMed  Google Scholar 

  26. Laulier C, Barascu A, Guirouilh-Barbat J, Pennarun G, Le Chalony C, Chevalier F, Palierne G, Bertrand P, Verbavatz JM, Lopez BS (2011) Bcl-2 inhibits nuclear homologous recombination by localizing BRCA1 to the endomembranes. Cancer Res 71(10):3590–3602

    Google Scholar 

  27. Lehembre F, Yilmaz M, Wicki A, Schomber T, Strittmatter K, Ziegler D, Kren A, Went P, Derksen PW, Berns A, Jonkers J, Christofori G (2008) NCAM-induced focal adhesion assembly: a functional switch upon loss of E-cadherin. EMBO J 27(19):2603–2615

    Article  PubMed  CAS  Google Scholar 

  28. Lehmann U, Streichert T, Otto B, Albat C, Hasemeier B, Christgen H, Schipper E, Hille U, Kreipe HH, Langer F (2010) Identification of differentially expressed microRNAs in human male breast cancer. BMC Cancer 10:109

    Google Scholar 

  29. Li G, Luna C, Qiu J, Epstein DL, Gonzalez P (2010) Targeting of integrin beta1 and kinesin 2alpha by microRNA 183. J Biol Chem 285(8):5461–5471

    Google Scholar 

  30. Li J, Liang SH, Lu X (2010) Potential role of ezrin and its related microRNA in ovarian cancer invasion and metastasis. Zhonghua Fu Chan Ke Za Zhi 45(10):787–792

    Google Scholar 

  31. Lowery AJ, Miller N, Dwyer RM, Kerin MJ (2010) Dysregulated miR-183 inhibits migration in breast cancer cells. BMC Cancer 10:502

    Google Scholar 

  32. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838

    Article  PubMed  CAS  Google Scholar 

  33. Luo Y, He DL, Ning L, Shen SL, Li L, Li X (2006) Hypoxia-inducible factor-1alpha induces the epithelial-mesenchymal transition of human prostatecancer cells. Chin Med J (Engl) 119(9):713–718

    CAS  Google Scholar 

  34. Ma Q, Yang L, Wang C, Yu YY, Zhou B, Zhou ZG (2011) Differential expression of colon cancer microRNA in microarray study. Sichuan Da Xue Xue Bao Yi Xue Ban 42(3):344–348

    Google Scholar 

  35. Miko E, Czimmerer Z, Csanky E, Boros G, Buslig J, Dezso B, Scholtz B (2009) Differentially expressed microRNAs in small cell lung cancer. Exp Lung Res 35(8):646–664

    Article  PubMed  CAS  Google Scholar 

  36. Moskwa P, Buffa FM, Pan Y, Panchakshari R, Gottipati P, Muschel RJ, Beech J, Kulshrestha R, Abdelmohsen K, Weinstock DM, Gorospe M, Harris AL, Helleday T, Chowdhury D (2011) miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol Cell 41(2):210–220

    Google Scholar 

  37. Motoyama K, Inoue H, Takatsuno Y, Tanaka F, Mimori K, Uetake H, Sugihara K, Mori M (2009) Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol 34(4):1069–1075

    PubMed  CAS  Google Scholar 

  38. Myatt SS, Wang J, Monteiro LJ, Christian M, Ho KK, Fusi L, Dina RE, Brosens JJ, Ghaem-Maghami S, Lam EW (2010) Definition of microRNAs that repress expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res 70(1):367–377

    Google Scholar 

  39. Nakajima S, Doi R, Toyoda E, Tsuji S, Wada M, Koizumi M, Tulachan SS, Ito D, Kami K, Mori T, Kawaguchi Y, Fujimoto K, Hosotani R, Imamura M (2004) N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma. Clin Cancer Res 10(12 Pt 1):4125–4133

    Google Scholar 

  40. Northcott PA, Fernandez LA, Hagan JP, Ellison DW, Grajkowska W, Gillespie Y, Grundy R, Van Meter T, Rutka JT, Croce CM, Kenney AM, Taylor MD (2009) The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursors. Cancer Res 69(8):3249–3255

    Article  PubMed  CAS  Google Scholar 

  41. Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, Bouffet E, Clifford SC, Hawkins CE, French P, Rutka JT, Pfister S, Taylor MD Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29(11):1408–1414

  42. Pantuck AJ, An J, Liu H, Rettig MB (2010) NF-kappaB-dependent plasticity of the epithelial to mesenchymal transition induced by Von Hippel-Lindau inactivation in renal cell carcinomas. Cancer Res 70(2):752–761

    Google Scholar 

  43. Pfister S, Remke M, Benner A, Mendrzyk F, Toedt G, Felsberg J, Wittmann A, Devens F, Gerber NU, Joos S, Kulozik A, Reifenberger G, Rutkowski S, Wiestler OD, Radlwimmer B, Scheurlen W, Lichter P, Korshunov A (2009) Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci. J Clin Oncol 27(10):1627–1636. doi:10.1200/JCO.2008.17.9432

    Article  PubMed  Google Scholar 

  44. Remke M, Hielscher T, Korshunov A, Northcott PA, Bender S, Kool M, Westermann F, Benner A, Cin H, Ryzhova M, Sturm D, Witt H, Haag D, Toedt G, Wittmann A, Schottler A, von Bueren AO, von Deimling A, Rutkowski S, Scheurlen W, Kulozik AE, Taylor MD, Lichter P, Pfister SM (2011) FSTL5 is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma. J Clin Oncol. doi:10.1200/JCO.2011.36.2798

  45. Remke M, Hielscher T, Northcott PA, Witt H, Ryzhova M, Wittmann A, Benner A, von Deimling A, Scheurlen W, Perry A, Croul S, Kulozik AE, Lichter P, Taylor MD, Pfister SM, Korshunov A (2011) Adult medulloblastoma comprises three major molecular variants. J Clin Oncol 29(19):2717–2723. doi:10.1200/JCO.2011.34.9373

    Article  PubMed  Google Scholar 

  46. Sacheli R, Nguyen L, Borgs L, Vandenbosch R, Bodson M, Lefebvre P, Malgrange B (2009) Expression patterns of miR-96, miR-182 and miR-183 in the development inner ear. Gene Expr Patterns 9(5):364–370

    Article  PubMed  CAS  Google Scholar 

  47. Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, Miller K, Lein M, Kristiansen G, Jung K (2010) Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer 126(5):1166–1176

    Google Scholar 

  48. Segura MF, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez-Diaz S, Zakrzewski J, Blochin E, Rose A, Bogunovic D, Polsky D, Wei J, Lee P, Belitskaya-Levy I, Bhardwaj N, Osman I, Hernando E (2009) Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci USA 106(6):1814–1819

    Article  PubMed  CAS  Google Scholar 

  49. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102(43):15545–15550

    Article  PubMed  CAS  Google Scholar 

  50. Sun S, Ning X, Zhang Y, Lu Y, Nie Y, Han S, Liu L, Du R, Xia L, He L, Fan D (2009) Hypoxia-inducible factor-1alpha induces Twist expression in tubular epithelial cells subjected to hypoxia, leading to epithelial-to-mesenchymal transition. Kidney Int 75(12):1278–1287

    Article  PubMed  CAS  Google Scholar 

  51. Tamayo P, Cho YJ, Tsherniak A, Greulich H, Ambrogio L, Schouten-van Meeteren N, Zhou T, Buxton A, Kool M, Meyerson M, Pomeroy SL, Mesirov JP (2011) Predicting relapse in patients with medulloblastoma by integrating evidence from clinical and genomic features. J Clin Oncol 29(11):1415–1423

    Google Scholar 

  52. Thompson MC, Fuller C, Hogg TL, Dalton J, Finkelstein D, Lau CC, Chintagumpala M, Adesina A, Ashley DM, Kellie SJ, Taylor MD, Curran T, Gajjar A, Gilbertson RJ (2006) Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 24(12):1924–1931

    Article  PubMed  CAS  Google Scholar 

  53. Vaksman O, Stavnes HT, Kaern J, Trope CG, Davidson B, Reich R (2011) miRNA profiling along tumour progression in ovarian carcinoma. J Cell Mol Med 15(7):1593–1602

    Google Scholar 

  54. Wang G, Mao W, Zheng S (2008) MicroRNA-183 regulates Ezrin expression in lung cancer cells. FEBS Lett 582(25–26):3663–3668

    Article  PubMed  CAS  Google Scholar 

  55. Wang H, Yang ES, Jiang J, Nowsheen S, Xia F (2010) DNA damage-induced cytotoxicity is dissociated from BRCA1’s DNA repair function but is dependent on its cytosolic accumulation. Cancer Res 70(15):6258–6267

    Google Scholar 

  56. Weeraratne SD, Amani V, Neiss A, Teider N, Scott DK, Pomeroy SL, Cho YJ (2011) miR-34a confers chemosensitivity through modulation of MAGE-A and p53 in medulloblastoma. Neuro Oncol 13(2):165–175. doi:10.1093/neuonc/noq179

    Google Scholar 

  57. Weston MD, Pierce ML, Jensen-Smith HC, Fritzsch B, Rocha-Sanchez S, Beisel KW, Soukup GA (2011) MicroRNA-183 family expression in hair cell development and requirement of microRNAs for hair cell maintenance and survival. Dev Dyn 240(4):808–819

    Google Scholar 

  58. Xu S, Witmer PD, Lumayag S, Kovacs B, Valle D (2007) MicroRNA (miRNA) transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster. J Biol Chem 282(34):25053–25066

    Article  PubMed  CAS  Google Scholar 

  59. Yamada Y, Enokida H, Kojima S, Kawakami K, Chiyomaru T, Tatarano S, Yoshino H, Kawahara K, Nishiyama K, Seki N, Nakagawa M (2011) miR-96 and miR-183 detection in urine serve as potential tumor markers of urothelial carcinoma: correlation with stage and grade, and comparison with urinary cytology. Cancer Sci 102(3):522–529

    Google Scholar 

  60. Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ, Teng SC, Wu KJ (2008) Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol 10(3):295–305

    Article  PubMed  CAS  Google Scholar 

  61. Yao K, Ye PP, Tan J, Tang XJ, Shen Tu XC (2008) Involvement of PI3K/Akt pathway in TGF-beta2-mediated epithelial mesenchymal transition in human lens epithelial cells. Ophthalmic Res 40(2):69–76

    Article  PubMed  CAS  Google Scholar 

  62. Yin Y, Li M, Li H, Jiang Y, Cao LY, Zhang HF, Xu XC (2010) Expressions of 6 microRNAs in prostate cancer. Zhonghua Nan Ke Xue 16(7):599–605

  63. Zhang L, Liu T, Huang Y, Liu J (2011) microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein. Int J Mol Med 28(3):381–388

    Google Scholar 

  64. Zhao JH, Luo Y, Jiang YG, He DL, Wu CT (2011) Knockdown of beta-Catenin through shRNA cause a reversal of EMT and metastatic phenotypes induced by HIF-1alpha. Cancer Invest 29(6):377–382

    Google Scholar 

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Acknowledgments

Y.J.C. is funded in part by the St. Baldrick’s Foundation Scholar Award and the Bear Necessities Pediatric Cancer Research Foundation. A.H.B. was funded in part by the German Academic Exchange. This project received support from Grant NIH-R01-CA109467.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology, Children’s Hospital Boston and Harvard Medical School, Boston, MA, 02115, USA

    Shyamal Dilhan Weeraratne, Vladimir Amani, Natalia Teider, Jessica Pierre-Francois, Min Jeong Kye, Soma Sengupta, Tenley Archer, Judith A. J. Steen, Scott L. Pomeroy & Yoon-Jae Cho

  2. Department of Pathology, Children’s Hospital Boston, Boston, MA, 02115, USA

    Dominic Winter, Min Jeong Kye, Peter Warren & Judith A. J. Steen

  3. German Cancer Research Center (DKFZ), Heidelberg, Germany

    Marc Remke, Alfa H. C. Bai & Stefan M. Pfister

  4. Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Marc Remke & Stefan M. Pfister

  5. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS Bldg, Rm P213, Stanford, CA, 94305, USA

    Yoon-Jae Cho

  6. Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Yoon-Jae Cho

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  1. Shyamal Dilhan Weeraratne
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Correspondence to Yoon-Jae Cho.

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Supplementary Figure legends

Figure S1. Submap of medulloblastoma cell line ‘clusters’ compared to molecular subtypes of primary medulloblastomas as defined in Cho et al. [10]. and Northcott et al. [41].

Figure S2. Increased senescence b-gal staining of D458 and D556 medulloblastoma cell lines upon knockdown of miR-183~96~182.

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Weeraratne, S.D., Amani, V., Teider, N. et al. Pleiotropic effects of miR-183~96~182 converge to regulate cell survival, proliferation and migration in medulloblastoma. Acta Neuropathol 123, 539–552 (2012). https://doi.org/10.1007/s00401-012-0969-5

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