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Role of MicroRNAs in Stem Cell Regulation and Tumorigenesis in Drosophila

  • Stephanie Rager
  • Brian Chan
  • Lyric Forney
  • Shree Ram SinghEmail author
Chapter

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that modulate the expression of target mRNA. They are involved in many biological processes such as developmental timing, differentiation, cell death, immune response, stem cell behavior, and cancer. Growing evidence suggests that miRNAs play vital roles in regulating several aspects of stem cell biology in Drosophila including cell division, self-renewal, and differentiation. In recent years, miRNAs have emerged as collaborating factors that promote the activity of oncogenes in tumor development. Here, we present a brief overview on the role of miRNAs in the regulation of stem cell behavior and tumorigenesis in Drosophila.

Keywords

MicroRNA Stem cells Tumorigenesis Drosophila 

Notes

Acknowledgements

This research was supported by the Intramural Research Program, National Cancer Institute of the National Institutes of Health. Lyric Forney is supported by Werner H. Kirsten Student Intern Program (WHK SIP) of National Cancer Institute at Frederick.

References

  1. 1.
    Plasterk RH. Micro RNAs in animal development. Cell. 2006;124:877–81.PubMedGoogle Scholar
  2. 2.
    Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007;318(5858):1931–4.PubMedGoogle Scholar
  3. 3.
    Flynt AS, Lai EC. Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet. 2008;9(11):831–42.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Gangaraju VK, Lin H. MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol. 2009;10(2):116–25.PubMedGoogle Scholar
  5. 5.
    Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002;21(17):4663–70.PubMedCentralPubMedGoogle Scholar
  6. 6.
    Thomson T, Lin H. The biogenesis and function of PIWI proteins and piRNAs: progress and prospect. Annu Rev Cell Dev Biol. 2009;25:355–76.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23(20):4051–60.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S, Kim VN. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425(6956):415–9.PubMedGoogle Scholar
  9. 9.
    Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary microRNAs by the Microprocessor complex. Nature. 2004;432(7014):231–5.PubMedGoogle Scholar
  10. 10.
    Landthaler M, Yalcin A, Tuschl T. The human DiGeorge syndrome critical region gene 8 and its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol. 2004;14(23):2162–7.PubMedGoogle Scholar
  11. 11.
    Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004;432(7014):235–40.PubMedGoogle Scholar
  12. 12.
    Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006;125(5):887–901.PubMedGoogle Scholar
  13. 13.
    Martin R, Smibert P, Yalcin A, Tyler DM, Schäfer U, Tuschl T, Lai EC. Drosophila pasha mutant distinguishes the canonical microRNA and mirtron pathways. Mol Cell Biol. 2009;29(3):861–70.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17(24):3011–6.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA. 2004;10(2):185–91.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Hutvágner G, McLachlan J, Pasquinelli AE, Bálint E, Tuschl T, Zamore PD. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001;293(5531):834–8.PubMedGoogle Scholar
  17. 17.
    Carmell MA, Hannon GJ. RNase III enzymes and the initiation of gene silencing. Nat Struct Mol Biol. 2004;11(3):214–8.PubMedGoogle Scholar
  18. 18.
    Zhang H, Kolb FA, Jaskiewicz L, Westhof E, Filipowicz W. Single processing center models for human Dicer and bacterial RNase III. Cell. 2004;118(1):57–68.PubMedGoogle Scholar
  19. 19.
    Saito K, Ishizuka A, Siomi H, Siomi MC. Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells. PLoS Biol. 2005;3(7):e235.PubMedCentralPubMedGoogle Scholar
  20. 20.
    Okamura K, Ishizuka A, Siomi H, Siomi MC. Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev. 2004;18(14):1655–66.PubMedCentralPubMedGoogle Scholar
  21. 21.
    Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, Shiekhattar R. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436(7051):740–4.PubMedCentralPubMedGoogle Scholar
  22. 22.
    Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.PubMedGoogle Scholar
  23. 23.
    Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75:855–62.PubMedGoogle Scholar
  24. 24.
    Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000;403:901–6.PubMedGoogle Scholar
  25. 25.
    Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. 2000;408:86–9.PubMedGoogle Scholar
  26. 26.
    Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853–8.PubMedGoogle Scholar
  27. 27.
    Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP. The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science. 2005;310(5755):1817–21.PubMedGoogle Scholar
  28. 28.
    Chen K, Rajewsky N. Natural selection on human microRNA binding sites inferred from SNP data. Nat Genet. 2006;38(12):1452–6.PubMedGoogle Scholar
  29. 29.
    Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19(1):92–105.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Berezikov E. Evolution of microRNA diversity and regulation in animals. Nat Rev Genet. 2011;12(12):846–60.PubMedGoogle Scholar
  31. 31.
    Berezikov E, Robine N, Samsonova A, Westholm JO, Naqvi A, Hung JH, Okamura K, Dai Q, Bortolamiol-Becet D, Martin R, Zhao Y, Zamore PD, Hannon GJ, Marra MA, Weng Z, Perrimon N, Lai EC. Deep annotation of Drosophila melanogaster microRNAs yields insights into their processing, modification, and emergence. Genome Res. 2011;21(2):203–15.PubMedCentralPubMedGoogle Scholar
  32. 32.
    Xia J, Zhang W. A meta-analysis revealed insights into the sources, conservation and impact of microRNA 5†²-isoforms in four model species. Nucleic Acids Res. 2013;1–15. doi:10.1093/nar/gkt967.Google Scholar
  33. 33.
    Mohammed J, Flynt AS, Siepel A, Lai EC. The impact of age, biogenesis, and genomic clustering on Drosophila microRNA evolution. RNA. 2013;19(9):1295–308.PubMedGoogle Scholar
  34. 34.
    O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10(2):111–22.PubMedGoogle Scholar
  35. 35.
    Fullaondo A, Lee SY. Identification of putative miRNA involved in Drosophila melanogaster immune response. Dev Comp Immunol. 2012;36(2):267–73.PubMedGoogle Scholar
  36. 36.
    Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, Horvitz HR, Kauppinen S, Plasterk RH. MicroRNA expression in zebrafish embryonic development. Science. 2005;309(5732):310–1.PubMedGoogle Scholar
  37. 37.
    Murchison EP, Partridge JF, Tam OH, Cheloufi S, Hannon GJ. Characterization of Dicer-deficient murine embryonic stem cells. Proc Natl Acad Sci U S A. 2005;102(34):12135–40.PubMedCentralPubMedGoogle Scholar
  38. 38.
    Jovanovic M, Hengartner MO. miRNAs and apoptosis: RNAs to die for. Oncogene. 2006;25(46):6176–87.PubMedGoogle Scholar
  39. 39.
    Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008;9(8):839–45.PubMedGoogle Scholar
  40. 40.
    Dumortier O, Hinault C, Van Obberghen E. MicroRNAs and metabolism crosstalk in energy homeostasis. Cell Metab. 2013;18(3):312–24.PubMedGoogle Scholar
  41. 41.
    Mathieu J, Ruohola-Baker H. Regulation of stem cell populations by microRNAs. Adv Exp Med Biol. 2013;786:329–51.PubMedCentralPubMedGoogle Scholar
  42. 42.
    Di Leva G, Croce CM. miRNA profiling of cancer. Curr Opin Genet Dev. 2013;23(1):3–11.PubMedCentralPubMedGoogle Scholar
  43. 43.
    Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;4(8):535–48.Google Scholar
  44. 44.
    He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM. A microRNA polycistron as a potential human oncogene. Nature. 2005;435(7043):828–33.PubMedGoogle Scholar
  45. 45.
    O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc regulated microRNAs modulate E2F1 expression. Nature. 2005;435(7043):839–43.PubMedGoogle Scholar
  46. 46.
    Lin H. Cell biology of stem cells: an enigma of asymmetry and self-renewal. J Cell Biol. 2008;180(2):257–60.PubMedCentralPubMedGoogle Scholar
  47. 47.
    Singh SR. Stem cell niche in tissue homeostasis, aging and cancer. Curr Med Chem. 2012;19(35):5965–74.PubMedGoogle Scholar
  48. 48.
    Förstemann K, Tomari Y, Du T, Vagin VV, Denli AM, Bratu DP, Klattenhoff C, Theurkauf WE, Zamore PD. Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. PLoS Biol. 2005;3(7):e236.PubMedCentralPubMedGoogle Scholar
  49. 49.
    Shcherbata HR, Hatfield S, Ward EJ, Reynolds S, Fischer KA, Ruohola-Baker H. The MicroRNA pathway plays a regulatory role in stem cell division. Cell Cycle. 2006;5(2):172–5.PubMedGoogle Scholar
  50. 50.
    Hatfield S, Ruohola-Baker H. microRNA and stem cell function. Cell Tissue Res. 2008;331(1):57–66.PubMedCentralPubMedGoogle Scholar
  51. 51.
    Stadler BM, Ruohola-Baker H. Small RNAs: keeping stem cells in line. Cell. 2008;132(4):563–6.PubMedCentralPubMedGoogle Scholar
  52. 52.
    Li Q, Gregory RI. MicroRNA regulation of stem cell fate. Cell Stem Cell. 2008;2(3):195–6.PubMedGoogle Scholar
  53. 53.
    Park JK, Liu X, Strauss TJ, McKearin DM, Liu Q. The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells. Curr Biol. 2007;17(6):533–8.PubMedGoogle Scholar
  54. 54.
    Wang Y, Baskerville S, Shenoy A, Babiarz JE, Baehner L, Blelloch R. Embryonic stem cell-specific microRNAs regulate the G1-S transition and promote rapid proliferation. Nat Genet. 2008;40(12):1478–83.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Murashov AK. A brief introduction to RNAi and microRNAs in stem cells. Methods Mol Biol. 2010;650:15–25.PubMedGoogle Scholar
  56. 56.
    Huang XA, Lin H. The microRNA regulation of stem cells. Wiley Interdiscip Rev Dev Biol. 2012;1(1):83–95.PubMedGoogle Scholar
  57. 57.
    Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H. Stem cell division is regulated by the microRNA pathway. Nature. 2005;435(7044):974–8.PubMedGoogle Scholar
  58. 58.
    Jiang F, Ye X, Liu X, Fincher L, McKearin D, Liu Q. Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. Genes Dev. 2005, 19(14):1674–9.PubMedCentralPubMedGoogle Scholar
  59. 59.
    Jin Z, Xie T. Dcr-1 maintains Drosophila ovarian stem cells. Curr Biol. 2007;17(6):539–44.PubMedGoogle Scholar
  60. 60.
    Shcherbata HR, Ward EJ, Fischer KA, Yu JY, Reynolds SH, Chen CH, Xu P, Hay BA, Ruohola-Baker H. Stage-specific differences in the requirements for germline stem cell maintenance in the Drosophila ovary. Cell Stem Cell. 2007;1(6):698–709.PubMedCentralPubMedGoogle Scholar
  61. 61.
    Yang L, Chen D, Duan R, Xia L, Wang J, Qurashi A, Jin P, Chen D. Argonaute 1 regulates the fate of germline stem cells in Drosophila. Development. 2007;134(23):4265–72.PubMedGoogle Scholar
  62. 62.
    Yang L, Duan R, Chen D, Wang J, Chen D, Jin P. Fragile X mental retardation protein modulates the fate of germline stem cells in Drosophila. Hum Mol Genet. 2007;16(15):1814–20.PubMedGoogle Scholar
  63. 63.
    Neumüller RA, Betschinger J, Fischer A, Bushati N, Poernbacher I, Mechtler K, Cohen SM, Knoblich JA. Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage. Nature. 2008;454(7201):241–5.PubMedCentralPubMedGoogle Scholar
  64. 64.
    Yang Y, Xu S, Xia L, Wang J, Wen S, Jin P, Chen D. The bantam microRNA is associated with Drosophila fragile X mental retardation protein and regulates the fate of germline stem cells. PLoS Genet. 2009;5(4):e1000444.PubMedCentralPubMedGoogle Scholar
  65. 65.
    Yu JY, Reynolds SH, Hatfield SD, Shcherbata HR, Fischer KA, Ward EJ, Long D, Ding Y, Ruohola-Baker H. Dicer-1-dependent Dacapo suppression acts downstream of Insulin receptor in regulating cell division of Drosophila germline stem cells. Development. 2009;136(9):1497–507.PubMedCentralPubMedGoogle Scholar
  66. 66.
    Azzam G, Smibert P, Lai EC, Liu JL. Drosophila Argonaute 1 and its miRNA biogenesis partners are required for oocyte formation and germline cell division. Dev Biol. 2012;365(2):384–94.PubMedCentralPubMedGoogle Scholar
  67. 67.
    Liu N, Han H, Lasko P. Vasa promotes Drosophila germline stem cell differentiation by activating mei-P26 translation by directly interacting with a (U)-rich motif in its 3′ UTR. Genes Dev. 2009;23(23):2742–52.PubMedCentralPubMedGoogle Scholar
  68. 68.
    Pek JW, Lim AK, Kai T. Drosophila maelstrom ensures proper germline stem cell lineage differentiation by repressing microRNA-7. Dev Cell. 2009;17(3):417–24.PubMedGoogle Scholar
  69. 69.
    Iovino N, Pane A, Gaul U. miR-184 has multiple roles in Drosophila female germline development. Dev Cell. 2009;17(1):123–33.PubMedGoogle Scholar
  70. 70.
    Wang H, Mu Y, Chen D. Effective gene silencing in Drosophila ovarian germline by artificial microRNAs. Cell Res. 2011;21(4):700–3.PubMedCentralPubMedGoogle Scholar
  71. 71.
    Li Y, Maines JZ, Tastan OY, McKearin DM, Buszczak M. Mei-P26 regulates the maintenance of ovarian germline stem cells by promoting BMP signaling. Development. 2012;139(9):1547–56.PubMedCentralPubMedGoogle Scholar
  72. 72.
    Toledano H, D’Alterio C, Czech B, Levine E, Jones DL. The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche. Nature. 2012;485(7400):605–10.PubMedGoogle Scholar
  73. 73.
    Eun SH, Stoiber PM, Wright HJ, McMurdie KE, Choi CH, Gan Q, Lim C, Chen X. MicroRNAs downregulate Bag of marbles to ensure proper terminal differentiation in the Drosophila male germline. Development. 2013;140(1):23–30.PubMedCentralPubMedGoogle Scholar
  74. 74.
    Pancratov R, Peng F, Smibert P, Yang S Jr, Olson ER, Guha-Gilford C, Kapoor AJ, Liang FX, Lai EC, Flaherty MS, DasgGupta R. The miR-310/13 cluster antagonizes β-catenin function in the regulation of germ and somatic cell differentiation in the Drosophila testis. Development. 2013;140(14):2904–16.PubMedGoogle Scholar
  75. 75.
    Joly W, Chartier A, Rojas-Rios P, Busseau I, Simonelig M. The CCR4 deadenylase acts with nanos and pumilio in the fine-tuning of Mei-P26 expression to promote germline stem cell self-renewal. Stem Cell Reports. 2013;1(5):411–24.PubMedCentralPubMedGoogle Scholar
  76. 76.
    Song X, Zhu CH, Doan C, Xie T. Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science. 2002;296(5574):1855–7.PubMedGoogle Scholar
  77. 77.
    Singh SR, Chen X, Hou SX. JAK/STAT signaling regulates tissue outgrowth and male germline stem cell fate in Drosophila. Cell Res. 2005;15(1):1–5.PubMedGoogle Scholar
  78. 78.
    Singh SR, Zheng Z, Wang H, Oh SW, Chen X, Hou SX. Competitiveness for the niche and mutual dependence of the germline and somatic stem cells in the Drosophila testis are regulated by the JAK/STAT signaling. J Cell Physiol. 2010;223(2):500–10.PubMedCentralPubMedGoogle Scholar
  79. 79.
    Wang H, Singh SR, Zheng Z, Oh SW, Chen X, Edwards K, Hou SX. Rap-GEF signaling controls stem cell anchoring to their niche through regulating DE-cadherin-mediated cell adhesion in the Drosophila testis. Dev Cell. 2006;10(1):117–26.PubMedGoogle Scholar
  80. 80.
    Singh SR, Zhen W, Zheng Z, Wang H, Oh SW, Liu W, Zbar B, Schmidt LS, Hou SX. The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance. Oncogene. 2006;25(44):5933–41.PubMedGoogle Scholar
  81. 81.
    Singh SR, Liu Y, Kango-Singh M, Nevo E. Genetic, immunofluorescence labeling, and in situ hybridization techniques in identification of stem cells in male and female germline niches. Methods Mol Biol. 2013;1035:9–23.PubMedGoogle Scholar
  82. 82.
    Fuller MT, Spradling AC. Male and female Drosophila germline stem cells: two versions of immortality. Science. 2007 Apr 20;316(5823):402–4.PubMedGoogle Scholar
  83. 83.
    Yamashita YM, Mahowald AP, Perlin JR, Fuller MT. Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science. 2007;315(5811):518–21.PubMedCentralPubMedGoogle Scholar
  84. 84.
    Matunis EL, Stine RR, de Cuevas M. Recent advances in Drosophila male germline stem cell biology. Spermatogenesis. 2012;2(3):137–44.PubMedCentralPubMedGoogle Scholar
  85. 85.
    Gönczy P, DiNardo S. The germ line regulates somatic cyst cell proliferation and fate during Drosophila spermatogenesis. Development. 1996;122(8):2437–47.PubMedGoogle Scholar
  86. 86.
    Voog J, D’Alterio C, Jones DL. Multipotent somatic stem cells contribute to the stem cell niche in the Drosophila testis. Nature. 2008;454(7208):1132–6.PubMedCentralPubMedGoogle Scholar
  87. 87.
    Weng R, Cohen SM. Drosophila miR-124 regulates neuroblast proliferation through its target anachronism. Development. 2012;139(8):1427–34.PubMedGoogle Scholar
  88. 88.
    Sun K, Westholm JO, Tsurudome K, Hagen JW, Lu Y, Kohwi M, Betel D, Gao FB, Haghighi AP, Doe CQ, Lai EC. Neurophysiological defects and neuronal gene deregulation in Drosophila mir-124 mutants. PLoS Genet. 2012;8(2):e1002515.PubMedCentralPubMedGoogle Scholar
  89. 89.
    Kucherenko MM, Barth J, Fiala A, Shcherbata HR. Steroid-induced microRNA let-7 acts as a spatio-temporal code for neuronal cell fate in the developing Drosophila brain. EMBO J. 2012;31(24):4511–23.PubMedCentralPubMedGoogle Scholar
  90. 90.
    Morante J, Vallejo DM, Desplan C, Dominguez M. Conserved miR-8/miR-200 defines a glial niche that controls neuroepithelial expansion and neuroblast transition. Dev Cell. 2013;27(2):174–87.PubMedGoogle Scholar
  91. 91.
    Huang H, Li J, Hu L, Ge L, Ji H, Zhao Y, Zhang L. Bantam is essential for Drosophila intestinal stem cell proliferation in response to Hippo signaling. Dev Biol. 2014;385(2):211–9. doi:10.1016/j.ydbio.2013.11.008.PubMedGoogle Scholar
  92. 92.
    Tokusumi T, Tokusumi Y, Hopkins DW, Shoue DA, Corona L, Schulz RA. Germ line differentiation factor Bag of Marbles is a regulator of hematopoietic progenitor maintenance during Drosophila hematopoiesis. Development. 2011;138(18):3879–84.PubMedCentralPubMedGoogle Scholar
  93. 93.
    Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.PubMedGoogle Scholar
  94. 94.
    Wang D, Qiu C, Zhang H, Wang J, Cui Q, Yin Y. Human microRNA oncogenes and tumor suppressors show significantly different biological patterns: from functions to targets. PLoS One. 2010;5(9):e13067.PubMedCentralPubMedGoogle Scholar
  95. 95.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.PubMedGoogle Scholar
  96. 96.
    Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10(10):704–14.PubMedCentralPubMedGoogle Scholar
  97. 97.
    Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28(3–4):369–78.PubMedGoogle Scholar
  98. 98.
    Costa PM, Pedroso de Lima MC. MicroRNAs as molecular targets for cancer therapy: on the modulation of microRNA expression. Pharmaceuticals. 2013;6(10):1195–220.PubMedCentralPubMedGoogle Scholar
  99. 99.
    Cheng AM, Byrom MW, Shelton J, et al. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res. 2005;33:1290–7.PubMedCentralPubMedGoogle Scholar
  100. 100.
    Kumar MS, Lu J, Mercer KL, et al. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007;39:673–7.PubMedGoogle Scholar
  101. 101.
    Rubin GM, Hong L, Brokstein P, Evans-Holm M, Frise E, Stapleton M, Harvey DA. A Drosophila complementary DNA resource. Science. 2000;287(5461):2222–4.PubMedGoogle Scholar
  102. 102.
    Hombría JC, Serras F. Why should we care about fly tumors? The case of JAK-STAT and EGFR cooperation in oncogenesis. JAKSTAT. 2013;2(2):e23203.PubMedCentralPubMedGoogle Scholar
  103. 103.
    Miles WO, Dyson NJ, Walker JA. Modeling tumor invasion and metastasis in Drosophila. Dis Model Mech. 2011;4(6):753–61.PubMedCentralPubMedGoogle Scholar
  104. 104.
    Stefanatos RK, Vidal M. Tumor invasion and metastasis in Drosophila: a bold past, a bright future. J Genet Genomics. 2011;38(10):431–8.PubMedGoogle Scholar
  105. 105.
    Polesello C, Roch F, Gobert V, Haenlin M, Waltzer L. Modeling cancers in Drosophila. Prog Mol Biol Transl Sci. 2011;100:51–82.PubMedGoogle Scholar
  106. 106.
    Rudrapatna VA, Cagan RL, Das TK. Drosophila cancer models. Dev Dyn. 2012;241(1):107–18.PubMedCentralPubMedGoogle Scholar
  107. 107.
    Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113(1):25–36.PubMedGoogle Scholar
  108. 108.
    Nolo R, Morrison CM, Tao C, Zhang X, Halder G. The bantam microRNA is a target of the hippo tumor-suppressor pathway. Curr Biol. 2006;16(19):1895–904.PubMedGoogle Scholar
  109. 109.
    Nairz K, Rottig C, Rintelen F, Zdobnov E, Moser M, Hafen E. Overgrowth caused by misexpression of a microRNA with dispensable wild-type function. Dev Biol. 2006;291(2):314–24.PubMedGoogle Scholar
  110. 110.
    Vallejo DM, Caparros E, Dominguez M. Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells. EMBO J. 2011;30(4):756–69.PubMedCentralPubMedGoogle Scholar
  111. 111.
    Oh H, Irvine KD. Cooperative regulation of growth by Yorkie and Mad through bantam. Dev Cell. 2011;20(1):109–22.PubMedCentralPubMedGoogle Scholar
  112. 112.
    Herranz H, Hong X, Hung NT, Voorhoeve PM, Cohen SM. Oncogenic cooperation between SOCS family proteins and EGFR identified using a Drosophila epithelial transformation model. Genes Dev 2012, 26:1602–11.PubMedCentralPubMedGoogle Scholar
  113. 113.
    Da Ros VG, Gutierrez-Perez I, Ferres-Marco D, Dominguez M. Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates notch-induced tumourigenesis. PLoS Biol. 2013;11(5):e1001554.PubMedCentralPubMedGoogle Scholar
  114. 114.
    Zhang Y, Lai ZC. Mob as tumor suppressor is regulated by bantam microRNA through a feedback loop for tissue growth control. Biochem Biophys Res Commun. 2013;439(4):438–42.PubMedGoogle Scholar
  115. 115.
    Thompson BJ, Cohen SM. The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila. Cell. 2006;126(4):767–74.PubMedGoogle Scholar
  116. 116.
    Peng HW, Slattery M, Mann RS. Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc. Genes Dev. 2009;23(19):2307–19.PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Stephanie Rager
    • 1
  • Brian Chan
    • 1
  • Lyric Forney
    • 1
  • Shree Ram Singh
    • 1
    Email author
  1. 1.Mouse Cancer Genetics Program, and Basic Research Laboratory, Center for Cancer ResearchNational Cancer InstituteFrederickUSA

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