Cellular and Molecular Life Sciences

, Volume 69, Issue 21, pp 3571–3585

MicroRNA-mediated gene regulations in human sarcomas

Multi-author review

Abstract

Sarcomas are a heterogeneous group of tumors with mesenchymal origins. Sarcomas are broadly classified into bone and soft tissue sarcomas with over 50 subtypes. Despite recent advances in sarcoma classification and treatment strategies, the prognosis of some aggressive sarcoma types remains poor due to treatment infectiveness and development of drug resistance. A better understanding of sarcoma pathobiology will significantly increase the potential for the development of therapeutics and treatment strategies. Recently, expressions of microRNAs (miRNA), a class of small non-coding RNAs, have been found to be deregulated in many sarcomas and are implicated in sarcoma pathobiology. Comprehensive understanding of gene regulatory networks mediated by miRNAs in each sarcoma type and the conservation of some shared/conserved miRNA-gene networks could be potentially investigated in the prevention, diagnosis, prognosis and as multi-modal treatment options in these cancers. In this review, we will discuss the current knowledge of miRNA–gene regulatory networks in various sarcoma types and give a perspective of the complex multilayer miRNA-mediated gene regulation in sarcomas.

Keywords

Sarcoma MicroRNA Soft tissue sarcoma Bone sarcoma Markers Expression Gene networks Osteosarcoma Rhabdomyosarcoma MPNSTs GIST Synovial sarcoma Liposarcoma 

References

  1. 1.
    Taylor BS, Barretina J, Maki RG, Antonescu CR, Singer S, Ladanyi M (2011) Advances in sarcoma genomics and new therapeutic targets. Nat Rev Cancer 11(8):541–557. doi:10.1038/nrc3087 PubMedGoogle Scholar
  2. 2.
    Fletcher CDM, Unni KK, Mertens F (2002) World Health Organization Classification of Tumors, Pathology and genetics of tumours of soft tissue and bone. IARC Press, LyonGoogle Scholar
  3. 3.
    Weiss S, Goldblum J (2008) Soft tissue tumors. Elsevier, MosbyGoogle Scholar
  4. 4.
    Dela Cruz F, Matushansky I (2011) MicroRNAs in chromosomal translocation-associated solid tumors: learning from sarcomas. Discov Med 12(65):307–317PubMedGoogle Scholar
  5. 5.
    Barr FG (1997) Molecular genetics and pathogenesis of rhabdomyosarcoma. J Pediatr Hematol Oncol 19(6):483–491PubMedGoogle Scholar
  6. 6.
    Riggi N, Cironi L, Suva ML, Stamenkovic I (2007) Sarcomas: genetics, signalling, and cellular origins part 1: the fellowship of TET. J Pathol 213(1):4–20. doi:10.1002/path.2209 PubMedGoogle Scholar
  7. 7.
    Brisset S, Schleiermacher G, Peter M, Mairal A, Oberlin O, Delattre O, Aurias A (2001) CGH analysis of secondary genetic changes in Ewing tumors: correlation with metastatic disease in a series of 43 cases. Cancer Genet Cytogenet 130(1):57–61PubMedGoogle Scholar
  8. 8.
    Mankin HJ, Hornicek FJ, Rosenberg AE, Harmon DC, Gebhardt MC (2004) Survival data for 648 patients with osteosarcoma treated at one institution. Clin Orthop Relat Res 429:286–291 (pii 00003086-200412000-00043)PubMedGoogle Scholar
  9. 9.
    Scurr M (2011) Histology-driven chemotherapy in soft tissue sarcomas. Curr Treat Options Oncol 12(1):32–45. doi:10.1007/s11864-011-0140-x PubMedGoogle Scholar
  10. 10.
    Subramanian S, West RB, Corless CL, Ou W, Rubin BP, Chu KM, Leung SY, Yuen ST, Zhu S, Hernandez-Boussard T, Montgomery K, Nielsen TO, Patel RM, Goldblum JR, Heinrich MC, Fletcher JA, van de Rijn M (2004) Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene 23(47):7780–7790PubMedGoogle Scholar
  11. 11.
    Subramanian S, West RB, Marinelli RJ, Nielsen TO, Rubin BP, Goldblum JR, Patel RM, Zhu S, Montgomery K, Ng TL, Corless CL, Heinrich MC, van de Rijn M (2005) The gene expression profile of extraskeletal myxoid chondrosarcoma. J Pathol 206(4):433–444PubMedGoogle Scholar
  12. 12.
    West RB, Rubin BP, Miller MA, Subramanian S, Kaygusuz G, Montgomery K, Zhu S, Marinelli RJ, De Luca A, Downs-Kelly E, Goldblum JR, Corless CL, Brown PO, Gilks CB, Nielsen TO, Huntsman D, van de Rijn M (2006) A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci USA 103(3):690–695. doi:10.1073/pnas.0507321103 PubMedGoogle Scholar
  13. 13.
    Nielsen TO, West RB, Linn SC, Alter O, Knowling MA, O’Connell JX, Zhu S, Fero M, Sherlock G, Pollack JR, Brown PO, Botstein D, van de Rijn M (2002) Molecular characterisation of soft tissue tumours: a gene expression study. Lancet 359(9314):1301–1307PubMedGoogle Scholar
  14. 14.
    Antonescu CR (2008) Molecular profiling in the diagnosis and treatment of high grade sarcomas. Ultrastruct Pathol 32(2):37–42. doi:10.1080/01913120801897174 PubMedGoogle Scholar
  15. 15.
    van de Rijn M, Fletcher JA (2006) Genetics of soft tissue tumors. Annu Rev Pathol 1:435–466. doi:10.1146/annurev.pathol.1.110304.100052 PubMedGoogle Scholar
  16. 16.
    Subramanian S, Lui WO, Lee CH, Espinosa I, Nielsen TO, Heinrich MC, Corless CL, Fire AZ, van de Rijn M (2008) MicroRNA expression signature of human sarcomas. Oncogene 27(14):2015–2026. doi:10.1038/sj.onc.1210836 PubMedGoogle Scholar
  17. 17.
    Sarver AL, Phalak R, Thayanithy V, Subramanian S (2010) S-MED: sarcoma microRNA expression database. Lab Invest J Techn Methods Pathol 90(5):753–761. doi:10.1038/labinvest.2010.53 Google Scholar
  18. 18.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297 (pii S0092867404000455)PubMedGoogle Scholar
  19. 19.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233PubMedGoogle Scholar
  20. 20.
    Bartel DP, Chen CZ (2004) Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet 5(5):396–400. doi:10.1038/nrg1328nrg1328 PubMedGoogle Scholar
  21. 21.
    Hobert O (2007) miRNAs play a tune. Cell 131(1):22–24PubMedGoogle Scholar
  22. 22.
    Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foa R, Schliwka J, Fuchs U, Novosel A, Muller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, Choksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129(7):1401–1414. doi:10.1016/j.cell.2007.04.040 PubMedGoogle Scholar
  23. 23.
    Li X, Cassidy JJ, Reinke CA, Fischboeck S, Carthew RW (2009) A microRNA imparts robustness against environmental fluctuation during development. Cell 137(2):273–282. doi:10.1016/j.cell.2009.01.058 PubMedGoogle Scholar
  24. 24.
    Mendell JT (2008) miRiad roles for the miR-17-92 cluster in development and disease. Cell 133(2):217–222PubMedGoogle Scholar
  25. 25.
    Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10(10):704–714. doi:10.1038/nrg2634 PubMedGoogle Scholar
  26. 26.
    Kim VN (2005) Small RNAs: classification, biogenesis, and function. Mol Cell 19(1):1–15 (Pii 806)Google Scholar
  27. 27.
    Flynt AS, Lai EC (2008) Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet 9(11):831–842. doi:10.1038/nrg2455 PubMedGoogle Scholar
  28. 28.
    Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355. doi:10.1038/nature02871 PubMedGoogle Scholar
  29. 29.
    Altuvia Y, Landgraf P, Lithwick G, Elefant N, Pfeffer S, Aravin A, Brownstein MJ, Tuschl T, Margalit H (2005) Clustering and conservation patterns of human microRNAs. Nucleic Acids Res 33(8):2697–2706. doi:10.1093/nar/gki567 PubMedGoogle Scholar
  30. 30.
    Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854PubMedGoogle Scholar
  31. 31.
    Eulalio A, Huntzinger E, Izaurralde E (2008) Getting to the root of miRNA-mediated gene silencing. Cell 132(1):9–14PubMedGoogle Scholar
  32. 32.
    Yekta S, Shih IH, Bartel DP (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304(5670):594–596PubMedGoogle Scholar
  33. 33.
    Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269PubMedGoogle Scholar
  34. 34.
    Sarver A, Li L, Subramanian S (2010) MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Can Res 70:9570–9580Google Scholar
  35. 35.
    Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6(11):857–866. doi:10.1038/nrc1997 PubMedGoogle Scholar
  36. 36.
    Subramanian S, Steer CJ (2010) MicroRNAs as gatekeepers of apoptosis. J Cell Physiol 223(2):289–298. doi:10.1002/jcp.22066 PubMedGoogle Scholar
  37. 37.
    Gabriely G, Wurdinger T, Kesari S, Esau CC, Burchard J, Linsley PS, Krichevsky AM (2008) MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol Cell Biol 28(17):5369–5380. doi:10.1128/MCB.00479-08MCB.00479-08 PubMedGoogle Scholar
  38. 38.
    Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, Egan DA, Li A, Huang G, Klein-Szanto AJ, Gimotty PA, Katsaros D, Coukos G, Zhang L, Pure E, Agami R (2008) The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 10(2):202–210PubMedGoogle Scholar
  39. 39.
    Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szasz AM, Wang ZC, Brock JE, Richardson AL, Weinberg RA (2009) A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 137(6):1032–1046. doi:10.1016/j.cell.2009.03.047 PubMedGoogle Scholar
  40. 40.
    Liu C, Tang DG (2011) MicroRNA regulation of cancer stem cells. Cancer Res 71(18):5950–5954. doi:10.1158/0008-5472.CAN-11-1035 PubMedGoogle Scholar
  41. 41.
    Xu N, Papagiannakopoulos T, Pan G, Thomson JA, Kosik KS (2009) MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 137(4):647–658. doi:10.1016/j.cell.2009.02.038 PubMedGoogle Scholar
  42. 42.
    Riggi N, Suva ML, De Vito C, Provero P, Stehle JC, Baumer K, Cironi L, Janiszewska M, Petricevic T, Suva D, Tercier S, Joseph JM, Guillou L, Stamenkovic I (2010) EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev 24(9):916–932. doi:10.1101/gad.1899710 PubMedGoogle Scholar
  43. 43.
    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. doi:10.1038/nature03702 PubMedGoogle Scholar
  44. 44.
    Greither T, Wurl P, Grochola L, Bond G, Bache M, Kappler M, Lautenschlager C, Holzhausen HJ, Wach S, Eckert AW, Taubert H (2012) Expression of microRNA 210 associates with poor survival and age of tumor onset of soft-tissue sarcoma patients. Int J Cancer 130(5):1230–1235. doi:10.1002/ijc.26109 PubMedGoogle Scholar
  45. 45.
    Thayanithy V, Sarver AL, Kartha RV, Li L, Angstadt AY, Breen M, Steer CJ, Modiano JF, Subramanian S (2012) Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma. Bone 50:171–181. doi:10.1016/j.bone.2011.10.012 PubMedGoogle Scholar
  46. 46.
    Maire G, Martin JW, Yoshimoto M, Chilton-MacNeill S, Zielenska M, Squire JA (2011) Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma. Cancer Genet 204(3):138–146. doi:10.1016/j.cancergen.2010.12.012 PubMedGoogle Scholar
  47. 47.
    Duan Z, Choy E, Harmon D, Liu X, Susa M, Mankin H, Hornicek FJ (2011) MicroRNA-199a-3p is down regulated in human osteosarcoma and regulates cell proliferation and migration. Mol Cancer Ther 10(8):1337–1345. doi:10.1158/1535-7163.MCT-11-0096 PubMedGoogle Scholar
  48. 48.
    Lulla RR, Costa FF, Bischof JM, Chou PM, de FBM, Vanin EF, Soares MB (2011) Identification of differentially expressed microRNAs in osteosarcoma. Sarcoma 2011:732690. doi:10.1155/2011/732690 PubMedGoogle Scholar
  49. 49.
    Jones KB, Salah Z, Del Mare S, Galasso M, Gaudio E, Nuovo GJ, Lovat F, Leblanc K, Palatini J, Randall RL, Volinia S, Stein GS, Croce CM, Lian JB, Aqeilan RI (2012) MicroRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. doi:10.1158/0008-5472.CAN-11-2663 Google Scholar
  50. 50.
    Osaki M, Takeshita F, Sugimoto Y, Kosaka N, Yamamoto Y, Yoshioka Y, Kobayashi E, Yamada T, Kawai A, Inoue T, Ito H, Oshimura M, Ochiya T MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression. Mol Ther 19 (6):1123–1130. doi:10.1038/mt.2011.53
  51. 51.
    Zhang H, Cai X, Wang Y, Tang H, Tong D, Ji F (2010) microRNA-143, down-regulated in osteosarcoma, promotes apoptosis and suppresses tumorigenicity by targeting Bcl-2. Oncol Rep 24(5):1363–1369PubMedGoogle Scholar
  52. 52.
    He C, Xiong J, Xu X, Lu W, Liu L, Xiao D, Wang D (2009) Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples. Biochem Biophys Res Commun 388(1):35–40. doi:10.1016/j.bbrc.2009.07.101 PubMedGoogle Scholar
  53. 53.
    Braun CJ, Zhang X, Savelyeva I, Wolff S, Moll UM, Schepeler T, Orntoft TF, Andersen CL, Dobbelstein M (2008) p53-Responsive micrornas 192 and 215 are capable of inducing cell cycle arrest. Cancer Res 68(24):10094–10104. doi:10.1158/0008-5472.CAN-08-1569 PubMedGoogle Scholar
  54. 54.
    Yan K, Gao J, Yang T, Ma Q, Qiu X, Fan Q, Ma B (2012) MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo. PLoS ONE 7(3):e33778. doi:10.1371/journal.pone.0033778 PubMedGoogle Scholar
  55. 55.
    Creighton CJ, Fountain MD, Yu Z, Nagaraja AK, Zhu H, Khan M, Olokpa E, Zariff A, Gunaratne PH, Matzuk MM, Anderson ML (2010) Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers. Cancer Res 70(5):1906–1915. doi:10.1158/0008-5472.CAN-09-3875 PubMedGoogle Scholar
  56. 56.
    Kobayashi E, Hornicek FJ, Duan Z (2012) MicroRNA involvement in osteosarcoma. Sarcoma 2012:359739. doi:10.1155/2012/359739 PubMedGoogle Scholar
  57. 57.
    Liu LH, Li H, Li JP, Zhong H, Zhang HC, Chen J, Xiao T (2011) miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3. Biochem Biophys Res Commun 416(1–2):31–38. doi:10.1016/j.bbrc.2011.10.117 PubMedGoogle Scholar
  58. 58.
    Ziyan W, Shuhua Y, Xiufang W, Xiaoyun L MicroRNA-21 is involved in osteosarcoma cell invasion and migration. Med Oncol doi:10.1007/s12032-010-9563-7
  59. 59.
    Kang HG, Kim HS, Kim KJ, Oh JH, Lee MR, Seol SM, Han I (2007) RECK expression in osteosarcoma: correlation with matrix metalloproteinases activation and tumor invasiveness. J Orthop Res 25(5):696–702. doi:10.1002/jor.20323 PubMedGoogle Scholar
  60. 60.
    Zhu J, Feng Y, Ke Z, Yang Z, Zhou J, Huang X, Wang L (2012) Down-regulation of miR-183 promotes migration and invasion of osteosarcoma by targeting ezrin. Am J Pathol. doi:10.1016/j.ajpath.2012.02.023 Google Scholar
  61. 61.
    Song B, Wang Y, Xi Y, Kudo K, Bruheim S, Botchkina GI, Gavin E, Wan Y, Formentini A, Kornmann M, Fodstad O, Ju J (2009) Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. Oncogene 28(46):4065–4074. doi:10.1038/onc.2009.274 PubMedGoogle Scholar
  62. 62.
    Song B, Wang Y, Titmus MA, Botchkina G, Formentini A, Kornmann M, Ju J (2010) Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells. Mol Cancer 9:96. doi:10.1186/1476-4598-9-96 PubMedGoogle Scholar
  63. 63.
    Gougelet A, Pissaloux D, Besse A, Perez J, Duc A, Dutour A, Blay JY, Alberti L (2011) Micro-RNA profiles in osteosarcoma as a predictive tool for ifosfamide response. Int J Cancer 129(3):680–690. doi:10.1002/ijc.25715 PubMedGoogle Scholar
  64. 64.
    Ban J, Jug G, Mestdagh P, Schwentner R, Kauer M, Aryee DN, Schaefer KL, Nakatani F, Scotlandi K, Reiter M, Strunk D, Speleman F, Vandesompele J, Kovar H (2011) Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing’s sarcoma. Oncogene 30(18):2173–2180. doi:10.1038/onc.2010.581 PubMedGoogle Scholar
  65. 65.
    McKinsey EL, Parrish JK, Irwin AE, Niemeyer BF, Kern HB, Birks DK, Jedlicka P (2011) A novel oncogenic mechanism in Ewing sarcoma involving IGF pathway targeting by EWS/Fli1-regulated microRNAs. Oncogene 30(49):4910–4920. doi:10.1038/onc.2011.197 PubMedGoogle Scholar
  66. 66.
    De Vito C, Riggi N, Suva ML, Janiszewska M, Horlbeck J, Baumer K, Provero P, Stamenkovic I (2011) Let-7a is a direct EWS-FLI-1 target implicated in Ewing’s sarcoma development. PLoS ONE 6(8):e23592. doi:10.1371/journal.pone.0023592 PubMedGoogle Scholar
  67. 67.
    Nakatani F, Ferracin M, Manara MC, Ventura S, Del Monaco V, Ferrari S, Alberghini M, Grilli A, Knuutila S, Schaefer KL, Mattia G, Negrini M, Picci P, Serra M, Scotlandi K (2012) miR-34a predicts survival of Ewing’s sarcoma patients and directly influences cell chemo-sensitivity and malignancy. J Pathol 226(5):796–805. doi:10.1002/path.3007 PubMedGoogle Scholar
  68. 68.
    Mosakhani N, Guled M, Leen G, Calabuig-Farinas S, Niini T, Machado I, Savola S, Scotlandi K, Lopez-Guerrero JA, Llombart-Bosch A, Knuutila S (2012) An integrated analysis of miRNA and gene copy numbers in xenografts of Ewing’s sarcoma. J Exp Clin Cancer Res CR 31(1):24. doi:10.1186/1756-9966-31-24 Google Scholar
  69. 69.
    Lin EA, Kong L, Bai XH, Luan Y, Liu CJ (2009) miR-199a, a bone morphogenic protein 2-responsive microRNA, regulates chondrogenesis via direct targeting to Smad1. J Biol Chem 284(17):11326–11335. doi:10.1074/jbc.M807709200 PubMedGoogle Scholar
  70. 70.
    Tuddenham L, Wheeler G, Ntounia-Fousara S, Waters J, Hajihosseini MK, Clark I, Dalmay T (2006) The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells. FEBS Lett 580(17):4214–4217. doi:10.1016/j.febslet.2006.06.080 PubMedGoogle Scholar
  71. 71.
    Zuntini M, Salvatore M, Pedrini E, Parra A, Sgariglia F, Magrelli A, Taruscio D, Sangiorgi L (2010) MicroRNA profiling of multiple osteochondromas: identification of disease-specific and normal cartilage signatures. Clin Genet 78(6):507–516. doi:10.1111/j.1399-0004.2010.01490.x PubMedGoogle Scholar
  72. 72.
    Hameetman L, Rozeman LB, Lombaerts M, Oosting J, Taminiau AH, Cleton-Jansen AM, Bovee JV, Hogendoorn PC (2006) Peripheral chondrosarcoma progression is accompanied by decreased Indian hedgehog signalling. J Pathol 209(4):501–511. doi:10.1002/path.2008 PubMedGoogle Scholar
  73. 73.
    Duan Z, Choy E, Nielsen GP, Rosenberg A, Iafrate J, Yang C, Schwab J, Mankin H, Xavier R, Hornicek FJ (2010) Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in Met expression. J Orthop Res 28(6):746–752. doi:10.1002/jor.21055 PubMedGoogle Scholar
  74. 74.
    Naka T, Iwamoto Y, Shinohara N, Ushijima M, Chuman H, Tsuneyoshi M (1997) Expression of c-met proto-oncogene product (c-MET) in benign and malignant bone tumors. Mod Pathol 10(8):832–838PubMedGoogle Scholar
  75. 75.
    Ostroumov E, Hunter CJ (2008) Identifying mechanisms for therapeutic intervention in chordoma: c-Met oncoprotein. Spine 33(25):2774–2780. doi:10.1097/BRS.0b013e31817e2d1e PubMedGoogle Scholar
  76. 76.
    Felli N, Fontana L, Pelosi E, Botta R, Bonci D, Facchiano F, Liuzzi F, Lulli V, Morsilli O, Santoro S, Valtieri M, Calin GA, Liu CG, Sorrentino A, Croce CM, Peschle C (2005) MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA 102(50):18081–18086. doi:10.1073/pnas.0506216102 PubMedGoogle Scholar
  77. 77.
    Fletcher JA, Rubin BP (2007) KIT mutations in GIST. Curr Opin Genet Dev 17(1):3–7. doi:10.1016/j.gde.2006.12.010 PubMedGoogle Scholar
  78. 78.
    Official Publication of the European Dialysis and Transplant Association-European Renal Association (1990) Abstracts of the Nephrology, dialysis, transplantation. Combined meeting of the Dutch Society of Nephrology and the Renal Association, Amsterdam, 27–28 October 1989Google Scholar
  79. 79.
    Kim WK, Park M, Kim YK, Tae YK, Yang HK, Lee JM, Kim H (2011) MicroRNA-494 downregulates KIT and inhibits gastrointestinal stromal tumor cell proliferation. Clin Cancer Res 17(24):7584–7594. doi:10.1158/1078-0432.CCR-11-0166 PubMedGoogle Scholar
  80. 80.
    Haller F, von Heydebreck A, Zhang JD, Gunawan B, Langer C, Ramadori G, Wiemann S, Sahin O (2009) Localization- and mutation-dependent microRNA (miRNA) expression signatures in gastrointestinal stromal tumours (GISTs), with a cluster of co-expressed miRNAs located at 14q32.31. J Pathol 220(1):71–86. doi:10.1002/path.2610 Google Scholar
  81. 81.
    Choi HJ, Lee H, Kim H, Kwon JE, Kang HJ, You KT, Rhee H, Noh SH, Paik YK, Hyung WJ, Kim H (2010) MicroRNA expression profile of gastrointestinal stromal tumors is distinguished by 14q loss and anatomic site. Int J Cancer 126(7):1640–1650. doi:10.1002/ijc.24897 PubMedGoogle Scholar
  82. 82.
    Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, Takamaru H, Yamamoto E, Maruyama R, Nobuoka T, Miyazaki Y, Nishida T, Bamba T, Kanda T, Ajioka Y, Taguchi T, Okahara S, Takahashi H, Nishida Y, Hosokawa M, Hasegawa T, Tokino T, Hirata K, Imai K, Toyota M, Shinomura Y (2012) Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res 72(5):1126–1136. doi:10.1158/0008-5472.CAN-11-1803 PubMedGoogle Scholar
  83. 83.
    Gurney JG, Davis S, Severson RK, Fang JY, Ross JA, Robison LL (1996) Trends in cancer incidence among children in the US. Cancer 78 (3):532–541. doi:10.1002/(SICI)1097-0142(19960801) Google Scholar
  84. 84.
    Qualman SJ, Coffin CM, Newton WA, Hojo H, Triche TJ, Parham DM, Crist WM (1998) Intergroup rhabdomyosarcoma study: update for pathologists. Pediatr Dev Pathol 1(6):550–561 (Pii PD-98-61)PubMedGoogle Scholar
  85. 85.
    Gougelet A, Perez J, Pissaloux D, Besse A, Duc A, Decouvelaere AV, Ranchere-Vince D, Blay JY, Alberti L (2011) miRNA Profiling: how to bypass the current difficulties in the diagnosis and treatment of sarcomas. Sarcoma 2011:460650. doi:10.1155/2011/460650 PubMedGoogle Scholar
  86. 86.
    Rota R, Ciarapica R, Giordano A, Miele L, Locatelli F (2011) MicroRNAs in rhabdomyosarcoma: pathogenetic implications and translational potentiality. Mol Cancer 10:120. doi:10.1186/1476-4598-10-120 PubMedGoogle Scholar
  87. 87.
    Rao PK, Missiaglia E, Shields L, Hyde G, Yuan B, Shepherd CJ, Shipley J, Lodish HF Distinct roles for miR-1 and miR-133a in the proliferation and differentiation of rhabdomyosarcoma cells. FASEB J 24 (9):3427–3437. doi:10.1096/fj.09-150698
  88. 88.
    Yan D, Dong XD, Chen X, Wang L, Lu C, Wang J, Qu J, Tu L (2009) MicroRNA-1/206 targets c-Met and inhibits rhabdomyosarcoma development. J Biol Chem. doi:10.1074/jbc.M109.020511 Google Scholar
  89. 89.
    Taulli R, Bersani F, Foglizzo V, Linari A, Vigna E, Ladanyi M, Tuschl T, Ponzetto C (2009) The muscle-specific microRNA miR-206 blocks human rhabdomyosarcoma growth in xenotransplanted mice by promoting myogenic differentiation. J Clin Invest 119(8):2366–2378. doi:10.1172/JCI38075 PubMedGoogle Scholar
  90. 90.
    Li L, Sarver AL, Alamgir S, Subramanian S (2012) Downregulation of microRNAs miR-1, -206 and -29 stabilizes PAX3 and CCND2 expression in rhabdomyosarcoma. Lab Invest 92(4):571–583. doi:10.1038/labinvest.2012.10 PubMedGoogle Scholar
  91. 91.
    Yan Z, Choi S, Liu X, Zhang M, Schageman JJ, Lee SY, Hart R, Lin L, Thurmond FA, Williams RS (2003) Highly coordinated gene regulation in mouse skeletal muscle regeneration. J Biol Chem 278(10):8826–8836. doi:10.1074/jbc.M209879200 PubMedGoogle Scholar
  92. 92.
    Baer C, Nees M, Breit S, Selle B, Kulozik AE, Schaefer KL, Braun Y, Wai D, Poremba C (2004) Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing’s sarcoma. Int J Cancer 110(5):687–694. doi:10.1002/ijc.20171 PubMedGoogle Scholar
  93. 93.
    Mayanil CS, George D, Freilich L, Miljan EJ, Mania-Farnell B, McLone DG, Bremer EG (2001) Microarray analysis detects novel Pax3 downstream target genes. J Biol Chem 276(52):49299–49309. doi:10.1074/jbc.M107933200 PubMedGoogle Scholar
  94. 94.
    Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, Croce CM, Guttridge DC (2008) NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 14(5):369–381PubMedGoogle Scholar
  95. 95.
    Ciarapica R, Russo G, Verginelli F, Raimondi L, Donfrancesco A, Rota R, Giordano A (2009) Deregulated expression of miR-26a and Ezh2 in rhabdomyosarcoma. Cell Cycle 8(1):172–175PubMedGoogle Scholar
  96. 96.
    Li Z, Hassan MQ, Jafferji M, Aqeilan RI, Garzon R, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2009) Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem 284(23):15676–15684. doi:10.1074/jbc.M809787200 PubMedGoogle Scholar
  97. 97.
    Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S, Guler G, Morrison CD, Chan KK, Marcucci G, Calin GA, Huebner K, Croce CM (2007) MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA 104(40):15805–15810PubMedGoogle Scholar
  98. 98.
    Gordon AT, Brinkschmidt C, Anderson J, Coleman N, Dockhorn-Dworniczak B, Pritchard-Jones K, Shipley J (2000) A novel and consistent amplicon at 13q31 associated with alveolar rhabdomyosarcoma. Genes Chromosomes Cancer 28(2):220–226PubMedGoogle Scholar
  99. 99.
    Reichek JL, Duan F, Smith LM, Gustafson DM, O’Connor RS, Zhang C, Dunlevy MJ, Gastier-Foster JM, Barr FG (2011) Genomic and clinical analysis of amplification of the 13q31 chromosomal region in alveolar rhabdomyosarcoma: a report from the children’s oncology group. Clin Cancer Res 17(6):1463–1473. doi:10.1158/1078-0432.CCR-10-0091 PubMedGoogle Scholar
  100. 100.
    Missiaglia E, Shepherd CJ, Patel S, Thway K, Pierron G, Pritchard-Jones K, Renard M, Sciot R, Rao P, Oberlin O, Delattre O, Shipley J MicroRNA-206 expression levels correlate with clinical behaviour of rhabdomyosarcomas. Br J Cancer 102 (12):1769–1777. doi:10.1038/sj.bjc.6605684
  101. 101.
    Miyachi M, Tsuchiya K, Yoshida H, Yagyu S, Kikuchi K, Misawa A, Iehara T, Hosoi H (2010) Circulating muscle-specific microRNA, miR-206, as a potential diagnostic marker for rhabdomyosarcoma. Biochem Biophys Res Commun 400(1):89–93. doi:10.1016/j.bbrc.2010.08.015 PubMedGoogle Scholar
  102. 102.
    Chen CF, He X, Arslan AD, Mo YY, Reinhold WC, Pommier Y, Beck WT (2011) Novel regulation of nuclear factor-YB by miR-485-3p affects the expression of DNA topoisomerase IIalpha and drug responsiveness. Mol Pharmacol 79(4):735–741. doi:10.1124/mol.110.069633 PubMedGoogle Scholar
  103. 103.
    Esau C, Kang X, Peralta E, Hanson E, Marcusson EG, Ravichandran LV, Sun Y, Koo S, Perera RJ, Jain R, Dean NM, Freier SM, Bennett CF, Lollo B, Griffey R (2004) MicroRNA-143 regulates adipocyte differentiation. J Biol Chem 279(50):52361–52365. doi:10.1074/jbc.C400438200 PubMedGoogle Scholar
  104. 104.
    Hisaoka M, Matsuyama A, Nagao Y, Luan L, Kuroda T, Akiyama H, Kondo S, Hashimoto H (2011) Identification of altered microRNA expression patterns in synovial sarcoma. Genes Chromosomes Cancer 50(3):137–145. doi:10.1002/gcc.20837 PubMedGoogle Scholar
  105. 105.
    Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38(2):228–233. doi:10.1038/ng1725 PubMedGoogle Scholar
  106. 106.
    Danielson LS, Menendez S, Attolini CS, Guijarro MV, Bisogna M, Wei J, Socci ND, Levine DA, Michor F, Hernando E (2010) A differentiation-based microRNA signature identifies leiomyosarcoma as a mesenchymal stem cell-related malignancy. Am J Pathol 177(2):908–917. doi:10.2353/ajpath.2010.091150 PubMedGoogle Scholar
  107. 107.
    Shi G, Perle MA, Mittal K, Chen H, Zou X, Narita M, Hernando E, Lee P, Wei JJ (2009) Let-7 repression leads to HMGA2 overexpression in uterine leiomyosarcoma. J Cell Mol Med 13 (9B):3898–3905. doi:10.1111/j.1582-4934.2008.00541.x Google Scholar
  108. 108.
    Nuovo GJ, Schmittgen TD (2008) Benign metastasizing leiomyoma of the lung: clinicopathologic, immunohistochemical, and micro-RNA analyses. Am J Surg Pathol B 17(3):145–150. doi:10.1097/PDM.0b013e31815aca19 Google Scholar
  109. 109.
    Ugras S, Brill E, Jacobsen A, Hafner M, Socci ND, Decarolis PL, Khanin R, O’Connor R, Mihailovic A, Taylor BS, Sheridan R, Gimble JM, Viale A, Crago A, Antonescu CR, Sander C, Tuschl T, Singer S (2011) Small RNA sequencing and functional characterization reveals microRNA-143 tumor suppressor activity in liposarcoma. Cancer Res 71(17):5659–5669. doi:10.1158/0008-5472.CAN-11-0890 PubMedGoogle Scholar
  110. 110.
    Zhang P, Bill K, Liu J, Young E, Peng T, Bolshakov S, Hoffman A, Song Y, Demicco EG, Terrada DL, Creighton CJ, Anderson ML, Lazar AJ, Calin GG, Pollock RE, Lev D (2012) MiR-155 is a liposarcoma oncogene that targets casein kinase-1alpha and enhances beta-catenin signaling. Cancer Res 72(7):1751–1762. doi:10.1158/0008-5472.CAN-11-3027 PubMedGoogle Scholar
  111. 111.
    Taylor BS, Decarolis PL, Angeles CV, Brenet F, Schultz N, Antonescu CR, Scandura JM, Sander C, Viale AJ, Socci ND, Singer S (2011) Frequent alterations and epigenetic silencing of differentiation pathway genes in structurally rearranged liposarcomas. Cancer Discov 1(7):587–597. doi:10.1158/2159-8290.CD-11-0181 PubMedGoogle Scholar
  112. 112.
    Subramanian S, Thayanithy V, West RB, Lee CH, Beck AH, Zhu S, Downs-Kelly E, Montgomery K, Goldblum JR, Hogendoorn PC, Corless CL, Oliveira AM, Dry SM, Nielsen TO, Rubin BP, Fletcher JA, Fletcher CD, van de Rijn M (2010) Genome-wide transcriptome analyses reveal p53 inactivation mediated loss of miR-34a expression in malignant peripheral nerve sheath tumours. J Pathol 220(1):58–70. doi:10.1002/path.2633 PubMedGoogle Scholar
  113. 113.
    Lee YB, Bantounas I, Lee DY, Phylactou L, Caldwell MA, Uney JB (2009) Twist-1 regulates the miR-199a/214 cluster during development. Nucleic Acids Res 37(1):123–128PubMedGoogle Scholar
  114. 114.
    Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939PubMedGoogle Scholar
  115. 115.
    Chai G, Liu N, Ma J, Li H, Oblinger JL, Prahalad AK, Gong M, Chang LS, Wallace M, Muir D, Guha A, Phipps RJ, Hock JM, Yu X (2010) MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1. Cancer Sci 101(9):1997–2004. doi:10.1111/j.1349-7006.2010.01616.x PubMedGoogle Scholar
  116. 116.
    Itani S, Kunisada T, Morimoto Y, Yoshida A, Sasaki T, Ito S, Ouchida M, Sugihara S, Shimizu K, Ozaki T (2012) MicroRNA-21 correlates with tumorigenesis in malignant peripheral nerve sheath tumor (MPNST) via programmed cell death protein 4 (PDCD4). J Cancer Res Clin Oncol. doi:10.1007/s00432-012-1223-1 PubMedGoogle Scholar
  117. 117.
    Pasmant E, Masliah-Planchon J, Levy P, Laurendeau I, Ortonne N, Parfait B, Valeyrie-Allanore L, Leroy K, Wolkenstein P, Vidaud M, Vidaud D, Bieche I (2011) Identification of genes potentially involved in the increased risk of malignancy in NF1-microdeleted patients. Mol Med 17(1–2):79–87. doi:10.2119/molmed.2010.00079 PubMedGoogle Scholar
  118. 118.
    Saydam O, Senol O, Wurdinger T, Mizrak A, Ozdener GB, Stemmer-Rachamimov AO, Yi M, Stephens RM, Krichevsky AM, Saydam N, Brenner GJ, Breakefield XO (2011) miRNA-7 attenuation in schwannoma tumors stimulates growth by upregulating three oncogenic signaling pathways. Cancer Res 71(3):852–861. doi:10.1158/0008-5472.CAN-10-1219 PubMedGoogle Scholar
  119. 119.
    Cioffi JA, Yue WY, Mendolia-Loffredo S, Hansen KR, Wackym PA, Hansen MR (2010) MicroRNA-21 overexpression contributes to vestibular schwannoma cell proliferation and survival. Otol Neurotol 31(9):1455–1462. doi:10.1097/MAO.0b013e3181f20655 PubMedGoogle Scholar
  120. 120.
    Liu P, Wilson MJ (2012) miR-520c and miR-373 upregulate MMP9 expression by targeting mTOR and SIRT1, and activate the Ras/Raf/MEK/Erk signaling pathway and NF-kappaB factor in human fibrosarcoma cells. J Cell Physiol 227(2):867–876. doi:10.1002/jcp.22993 PubMedGoogle Scholar
  121. 121.
    Weng C, Dong H, Chen G, Zhai Y, Bai R, Hu H, Lu L, Xu Z (2012) miR-409-3p inhibits HT1080 cell proliferation, vascularization and metastasis by targeting angiogenin. Cancer Lett. doi:10.1016/j.canlet.2012.04.010 PubMedGoogle Scholar
  122. 122.
    He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, Jackson AL, Linsley PS, Chen C, Lowe SW, Cleary MA, Hannon GJ (2007) A microRNA component of the p53 tumour suppressor network. Nature 447(7148):1130–1134. doi:10.1038/nature05939 PubMedGoogle Scholar
  123. 123.
    Park SY, Lee JH, Ha M, Nam JW, Kim VN (2009) miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42. Nat Struct Mol Biol 16(1):23–29PubMedGoogle Scholar
  124. 124.
    Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM, Marcucci G (2009) MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 113(25):6411–6418. doi:10.1182/blood-2008-07-170589 PubMedGoogle Scholar
  125. 125.
    Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, Denicola G, Webster KA, Weiss D, Perez-Mancera PA, Krauthammer M, Halaban R, Provero P, Adams DJ, Tuveson DA, Pandolfi PP (2011) In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell 147(2):382–395. doi:10.1016/j.cell.2011.09.032 PubMedGoogle Scholar

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  1. 1.Department of SurgeryUniversity of MinnesotaMinneapolisUSA
  2. 2.Masonic Cancer CenterUniversity of MinnesotaMinneapolisUSA
  3. 3.Department of Experimental and Clinical PharmacologyUniversity of MinnesotaMinneapolisUSA

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