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MicroRNAs in breast cancer initiation and progression

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Abstract

The emerging role of microRNAs (miRNAs) in the epigenetic regulation of many cellular processes has become recognized in both basic research and translational medicine as an important way that gene expression can be fine-tuned. Breast cancer is the most frequent cancer in women, with about one million new cases diagnosed each year worldwide. Starting with the early work of miRNA profiling, more effort has now been put on functions of miRNAs in normal mammary stem cells, breast cancer initiating cells and metastatic cells, and therapy-resistant cancer cells. Future translational studies may focus on identifying miRNA signatures as cancer biomarkers and developing miRNA-based targeted therapeutics.

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References

  1. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297 pii:S0092867404000455

    PubMed  CAS  Google Scholar 

  2. Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355. doi:10.1038/nature02871

    PubMed  CAS  Google Scholar 

  3. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, Allgayer H (2008) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27(15):2128–2136

    PubMed  CAS  Google Scholar 

  4. 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):202–210

    PubMed  CAS  Google Scholar 

  5. Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449(7163):682–688

    PubMed  CAS  Google Scholar 

  6. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massague J (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451(7175):147–152

    PubMed  CAS  Google Scholar 

  7. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10(5):593–601

    PubMed  CAS  Google Scholar 

  8. Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, Brabletz T (2008) A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep 9(6):582–589. doi:10.1038/embor.2008.74

    PubMed  CAS  Google Scholar 

  9. Park SM, Gaur AB, Lengyel E, Peter ME (2008) The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 22(7):894–907

    PubMed  CAS  Google Scholar 

  10. Korpal M, Lee ES, Hu G, Kang Y (2008) The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem 283(22):14910–14914. doi:10.1074/jbc.C800074200

    PubMed  CAS  Google Scholar 

  11. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10:593–601

    Google Scholar 

  12. Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, Dirbas FM, Somlo G, Pera RA, Lao K, Clarke MF (2009) Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138(3):592–603

    PubMed  CAS  Google Scholar 

  13. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, Song E (2007) Let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131(6):1109–1123

    PubMed  CAS  Google Scholar 

  14. Hurst DR, Edmonds MD, Welch DR (2009) Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Res 69(19):7495–7498

    PubMed  CAS  Google Scholar 

  15. Guo X, Wu Y, Hartley RS (2009) MicroRNA-125a represses cell growth by targeting HuR in breast cancer. RNA Biol 6(5):575–583

    PubMed  CAS  Google Scholar 

  16. Shipitsin M, Polyak K (2008) The cancer stem cell hypothesis: in search of definitions, markers, and relevance. Lab Invest 88(5):459–463. doi:10.1038/labinvest.2008.14

    PubMed  CAS  Google Scholar 

  17. Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439(7079):993–997. doi:10.1038/nature04496

    PubMed  CAS  Google Scholar 

  18. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE (2006) Generation of a functional mammary gland from a single stem cell. Nature 439(7072):84–88. doi:10.1038/nature04372

    PubMed  CAS  Google Scholar 

  19. Eirew P, Stingl J, Raouf A, Turashvili G, Aparicio S, Emerman JT, Eaves CJ (2008) A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability. Nat Med 14(12):1384–1389. doi:10.1038/nm.1791

    PubMed  CAS  Google Scholar 

  20. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555–567. doi:10.1016/j.stem.2007.08.014

    PubMed  CAS  Google Scholar 

  21. Van Keymeulen A, Rocha AS, Ousset M, Beck B, Bouvencourt G, Rock J, Sharma N, Dekoninck S, Blanpain C (2011) Distinct stem cells contribute to mammary gland development and maintenance. Nature 479(7372):189–193. doi:10.1038/nature10573

    PubMed  Google Scholar 

  22. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, Waldvogel B, Vannier C, Darling D, zur Hausen A, Brunton VG, Morton J, Sansom O, Schuler J, Stemmler MP, Herzberger C, Hopt U, Keck T, Brabletz S, Brabletz T (2009) The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 11 (12):1487–1495. doi:10.1038/ncb1998

    Google Scholar 

  23. Hyun S, Lee JH, Jin H, Nam J, Namkoong B, Lee G, Chung J, Kim VN (2009) Conserved microRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell 139(6):1096–1108. doi:10.1016/j.cell.2009.11.020

    PubMed  CAS  Google Scholar 

  24. Ibarra I, Erlich Y, Muthuswamy SK, Sachidanandam R, Hannon GJ (2007) A role for microRNAs in maintenance of mouse mammary epithelial progenitor cells. Genes Dev 21(24):3238–3243. doi:10.1101/gad.1616307

    PubMed  CAS  Google Scholar 

  25. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403(6772):901–906. doi:10.1038/35002607

    PubMed  CAS  Google Scholar 

  26. Bussing I, Slack FJ, Grosshans H (2008) Let-7 microRNAs in development, stem cells and cancer. Trends Mol Med 14(9):400–409. doi:10.1016/j.molmed.2008.07.001

    PubMed  Google Scholar 

  27. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ (2005) RAS is regulated by the let-7 microRNA family. Cell 120(5):635–647. doi:10.1016/j.cell.2005.01.014

    PubMed  CAS  Google Scholar 

  28. Greene SB, Gunaratne PH, Hammond SM, Rosen JM (2010) A putative role for microRNA-205 in mammary epithelial cell progenitors. J Cell Sci 123(Pt 4):606–618. doi:10.1242/jcs.056812

    PubMed  CAS  Google Scholar 

  29. Greene SB, Herschkowitz JI, Rosen JM (2010) The ups and downs of miR-205: identifying the roles of miR-205 in mammary gland development and breast cancer. RNA Biol 7(3):300–304 pii:11837

    PubMed  CAS  Google Scholar 

  30. Wang C, Li Q (2007) Identification of differentially expressed microRNAs during the development of Chinese murine mammary gland. J Genet Genomics 34(11):966–973. doi:10.1016/S1673-8527(07)60109-X

    PubMed  CAS  Google Scholar 

  31. Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM (2004) An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci USA 101(26):9740–9744

    PubMed  CAS  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. doi:10.1038/nature03702

    PubMed  CAS  Google Scholar 

  33. Cummins JM, He Y, Leary RJ, Pagliarini R, Diaz LA Jr, Sjoblom T, Barad O, Bentwich Z, Szafranska AE, Labourier E, Raymond CK, Roberts BS, Juhl H, Kinzler KW, Vogelstein B, Velculescu VE (2006) The colorectal microRNAome. Proc Natl Acad Sci USA 103(10):3687–3692

    PubMed  CAS  Google Scholar 

  34. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101–1108

    PubMed  CAS  Google Scholar 

  35. 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

    PubMed  CAS  Google Scholar 

  36. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev 6(11):857–866

    CAS  Google Scholar 

  37. Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev 10(10):704–714

    CAS  Google Scholar 

  38. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103(7):2257–2261

    PubMed  CAS  Google Scholar 

  39. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65(16):7065–7070. doi:10.1158/0008-5472.CAN-05-1783

    PubMed  CAS  Google Scholar 

  40. 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

    PubMed  CAS  Google Scholar 

  41. Prat A, Perou CM (2011) Deconstructing the molecular portraits of breast cancer. Mol Oncol 5(1):5–23. doi:10.1016/j.molonc.2010.11.003

    PubMed  CAS  Google Scholar 

  42. Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X, Perou CM (2010) Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 12(5):R68. doi:10.1186/bcr2635

    PubMed  Google Scholar 

  43. Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ, Barbosa-Morais NL, Teschendorff AE, Green AR, Ellis IO, Tavare S, Caldas C, Miska EA (2007) MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 8(10):R214. doi:10.1186/gb-2007-8-10-r214

    PubMed  Google Scholar 

  44. Buffa FM, Camps C, Winchester L, Snell CE, Gee HE, Sheldon H, Taylor M, Harris AL, Ragoussis J (2011) MicroRNA-associated progression pathways and potential therapeutic targets identified by integrated mRNA and microRNA expression profiling in breast cancer. Cancer Res 71(17):5635–5645

    PubMed  CAS  Google Scholar 

  45. Bockhorn J, Dalton R, Nwachukwu C, Prat A, Yee K, Chang Y-F, Huo D, Wen Y, Huang S, Swanson KE, Qiu T, Lu J, Park SY, Dolan ME, Perou CM, Olopade OI, Clarke MF, Greene GL, Liu H (2012) MicroRNA-30c inhibits human breast tumor chemotherapy resistance. Nat Commun (submitted)

  46. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100(7):3983–3988

    PubMed  CAS  Google Scholar 

  47. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120):756–760

    PubMed  CAS  Google Scholar 

  48. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3(7):730–737

    PubMed  CAS  Google Scholar 

  49. Cho RW, Wang X, Diehn M, Shedden K, Chen GY, Sherlock G, Gurney A, Lewicki J, Clarke MF (2008) Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors. Stem Cells 26(2):364–371

    PubMed  CAS  Google Scholar 

  50. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65(23):10946–10951

    PubMed  CAS  Google Scholar 

  51. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 104(24):10158–10163

    PubMed  CAS  Google Scholar 

  52. Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65(20):9328–9337

    PubMed  CAS  Google Scholar 

  53. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1(3):313–323

    PubMed  CAS  Google Scholar 

  54. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67(3):1030–1037

    PubMed  CAS  Google Scholar 

  55. Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, Zheng BJ, Guan XY (2007) Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 132(7):2542–2556

    PubMed  CAS  Google Scholar 

  56. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110

    PubMed  Google Scholar 

  57. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 104(3):973–978

    PubMed  CAS  Google Scholar 

  58. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115

    PubMed  CAS  Google Scholar 

  59. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828

    PubMed  CAS  Google Scholar 

  60. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648

    PubMed  CAS  Google Scholar 

  61. Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF (2007) The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med 356(3):217–226

    PubMed  CAS  Google Scholar 

  62. Liu H, Patel MR, Prescher JA, Patsialou A, Qian D, Lin J, Wen S, Chang YF, Bachmann MH, Shimono Y, Dalerba P, Adorno M, Lobo N, Bueno J, Dirbas FM, Goswami S, Somlo G, Condeelis J, Contag CH, Gambhir SS, Clarke MF (2010) Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proc Natl Acad Sci USA 107(42):18115–18120

    PubMed  CAS  Google Scholar 

  63. Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, Wong H, Rosen J, Chang JC (2008) Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 100(9):672–679. doi:10.1093/jnci/djn123

    PubMed  CAS  Google Scholar 

  64. Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, Qian D, Lam JS, Ailles LE, Wong M, Joshua B, Kaplan MJ, Wapnir I, Dirbas FM, Somlo G, Garberoglio C, Paz B, Shen J, Lau SK, Quake SR, Brown JM, Weissman IL, Clarke MF (2009) Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458(7239):780–783

    PubMed  CAS  Google Scholar 

  65. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715

    PubMed  CAS  Google Scholar 

  66. Iliopoulos D, Lindahl-Allen M, Polytarchou C, Hirsch HA, Tsichlis PN, Struhl K (2010) Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells. Mol Cell 39(5):761–772. doi:10.1016/j.molcel.2010.08.013

    PubMed  CAS  Google Scholar 

  67. Lee YS, Dutta A (2007) The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 21(9):1025–1030

    PubMed  CAS  Google Scholar 

  68. Yu F, Deng H, Yao H, Liu Q, Su F, Song E (2010) Mir-30 reduction maintains self-renewal and inhibits apoptosis in breast tumor-initiating cells. Oncogene 29(29):4194–4204. doi:10.1038/onc.2010.167

    PubMed  CAS  Google Scholar 

  69. Wang Y, Yu Y, Tsuyada A, Ren X, Wu X, Stubblefield K, Rankin-Gee EK, Wang SE (2011) Transforming growth factor-beta regulates the sphere-initiating stem cell-like feature in breast cancer through miRNA-181 and ATM. Oncogene 30(12):1470–1480

    PubMed  CAS  Google Scholar 

  70. Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, Liu MF, Wang ED (2010) MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res 70(8):3119–3127. doi:10.1158/0008-5472.CAN-09-4250

    PubMed  CAS  Google Scholar 

  71. Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12(8):895–904

    PubMed  CAS  Google Scholar 

  72. Lee YT (1983) Breast carcinoma: pattern of metastasis at autopsy. J Surg Oncol 23(3):175–180

    PubMed  CAS  Google Scholar 

  73. Weigelt B, Peterse JL, van ‘t Veer LJ (2005) Breast cancer metastasis: markers and models. Nat Rev 5 (8):591–602. doi:10.1038/nrc1670

    Google Scholar 

  74. Gee HE, Camps C, Buffa FM, Colella S, Sheldon H, Gleadle JM, Ragoussis J, Harris AL (2008) MicroRNA-10b and breast cancer metastasis. Nature 455(7216):E8–E9 author reply E9

    PubMed  CAS  Google Scholar 

  75. Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 4(1):33–45

    PubMed  CAS  Google Scholar 

  76. Gunthert U, Hofmann M, Rudy W, Reber S, Zoller M, Haussmann I, Matzku S, Wenzel A, Ponta H, Herrlich P (1991) A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65(1):13–24

    PubMed  CAS  Google Scholar 

  77. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE (2006) Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 12(10):1167–1174

    PubMed  Google Scholar 

  78. Weber GF, Bronson RT, Ilagan J, Cantor H, Schmits R, Mak TW (2002) Absence of the CD44 gene prevents sarcoma metastasis. Cancer Res 62(8):2281–2286

    PubMed  CAS  Google Scholar 

  79. Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, Enzo E, Guzzardo V, Rondina M, Spruce T, Parenti AR, Daidone MG, Bicciato S, Piccolo S (2010) A MicroRNA targeting dicer for metastasis control. Cell 141(7):1195–1207. doi:10.1016/j.cell.2010.05.017

    PubMed  CAS  Google Scholar 

  80. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY (2008) MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 18(3):350–359

    PubMed  CAS  Google Scholar 

  81. Li XF, Yan PJ, Shao ZM (2009) Downregulation of miR-193b contributes to enhance urokinase-type plasminogen activator (uPA) expression and tumor progression and invasion in human breast cancer. Oncogene 28(44):3937–3948

    PubMed  CAS  Google Scholar 

  82. 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

    PubMed  CAS  Google Scholar 

  83. Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celia-Terrassa T, Mercatali L, Khan Z, Goodarzi H, Hua Y, Wei Y, Hu G, Garcia BA, Ragoussis J, Amadori D, Harris AL, Kang Y (2011) Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med 17(9):1101–1108

    PubMed  CAS  Google Scholar 

  84. Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, Fan C, Zhang X, He X, Pavlick A, Gutierrez MC, Renshaw L, Larionov AA, Faratian D, Hilsenbeck SG, Perou CM, Lewis MT, Rosen JM, Chang JC (2009) Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 106(33):13820–13825

    PubMed  CAS  Google Scholar 

  85. Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S, Majumder S (2008) MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem 283(44):29897–29903. doi:10.1074/jbc.M804612200

    PubMed  CAS  Google Scholar 

  86. Zhao JJ, Lin J, Yang H, Kong W, He L, Ma X, Coppola D, Cheng JQ (2008) MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem 283(45):31079–31086

    PubMed  CAS  Google Scholar 

  87. Zhou M, Liu Z, Zhao Y, Ding Y, Liu H, Xi Y, Xiong W, Li G, Lu J, Fodstad O, Riker AI, Tan M (2010) MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression. J Biol Chem 285(28):21496–21507

    PubMed  CAS  Google Scholar 

  88. Kovalchuk O, Filkowski J, Meservy J, Ilnytskyy Y, Tryndyak VP, Chekhun VF, Pogribny IP (2008) Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther 7(7):2152–2159. doi:10.1158/1535-7163.MCT-08-0021

    PubMed  CAS  Google Scholar 

  89. Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI, Kovalchuk O (2010) Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer 127(8):1785–1794

    PubMed  CAS  Google Scholar 

  90. Yang H, Kong W, He L, Zhao JJ, O’Donnell JD, Wang J, Wenham RM, Coppola D, Kruk PA, Nicosia SV, Cheng JQ (2008) MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 68(2):425–433

    PubMed  CAS  Google Scholar 

  91. Weidhaas JB, Babar I, Nallur SM, Trang P, Roush S, Boehm M, Gillespie E, Slack FJ (2007) MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Res 67(23):11111–11116. doi:10.1158/0008-5472.CAN-07-2858

    PubMed  CAS  Google Scholar 

  92. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101(9):2999–3004. doi:10.1073/pnas.0307323101

    PubMed  CAS  Google Scholar 

  93. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99(24):15524–15529

    PubMed  CAS  Google Scholar 

  94. Scott GK, Mattie MD, Berger CE, Benz SC, Benz CC (2006) Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res 66(3):1277–1281. doi:10.1158/0008-5472.CAN-05-3632

    PubMed  CAS  Google Scholar 

  95. Png KJ, Yoshida M, Zhang XH, Shu W, Lee H, Rimner A, Chan TA, Comen E, Andrade VP, Kim SW, King TA, Hudis CA, Norton L, Hicks J, Massague J, Tavazoie SF (2011) MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer. Genes Dev 25(3):226–231. doi:10.1101/gad.1974211

    PubMed  CAS  Google Scholar 

  96. O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435(7043):839–843. doi:10.1038/nature03677

    PubMed  Google Scholar 

  97. Rokavec M, Wu W, Luo JL (2012) IL6-mediated suppression of miR-200c directs constitutive activation of inflammatory signaling circuit driving transformation and tumorigenesis. Mol Cell 45(6):777–789. doi:10.1016/j.molcel.2012.01.015

    PubMed  CAS  Google Scholar 

  98. Dedes KJ, Natrajan R, Lambros MB, Geyer FC, Lopez-Garcia MA, Savage K, Jones RL, Reis-Filho JS (2011) Down-regulation of the miRNA master regulators Drosha and Dicer is associated with specific subgroups of breast cancer. Eur J Cancer 47(1):138–150. doi:10.1016/j.ejca.2010.08.007

    PubMed  CAS  Google Scholar 

  99. Viswanathan SR, Daley GQ, Gregory RI (2008) Selective blockade of microRNA processing by Lin28. Science 320 (5872):97–100

    Google Scholar 

  100. Newman MA, Thomson JM, Hammond SM (2008) Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA 14 (8):1539–1549

    Google Scholar 

  101. Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, Teruya-Feldstein J, Bell GW, Weinberg RA (2010) Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol 28(4):341–347. doi:10.1038/nbt.1618

    PubMed  CAS  Google Scholar 

  102. Scherr M, Venturini L, Battmer K, Schaller-Schoenitz M, Schaefer D, Dallmann I, Ganser A, Eder M (2007) Lentivirus-mediated antagomir expression for specific inhibition of miRNA function. Nucleic Acids Res 35(22):e149. doi:10.1093/nar/gkm971

    PubMed  Google Scholar 

  103. Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, Mendell JR, Mendell JT (2009) Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137(6):1005–1017. doi:10.1016/j.cell.2009.04.021

    PubMed  CAS  Google Scholar 

  104. Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476. doi:10.1038/ncb1800

    PubMed  CAS  Google Scholar 

  105. Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, Tetta C, Camussi G (2010) Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One 5(7):e11803. doi:10.1371/journal.pone.0011803

    PubMed  Google Scholar 

  106. Chen X, Liang H, Zhang J, Zen K, Zhang CY (2012) Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol 22(3):125–132. doi:10.1016/j.tcb.2011.12.001

    PubMed  CAS  Google Scholar 

  107. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13(4):423–433. doi:10.1038/ncb2210

    PubMed  CAS  Google Scholar 

  108. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438(7068):685–689. doi:10.1038/nature04303

    PubMed  Google Scholar 

  109. Davis S, Lollo B, Freier S, Esau C (2006) Improved targeting of miRNA with antisense oligonucleotides. Nucleic Acids Res 34(8):2294–2304. doi:10.1093/nar/gkl183

    PubMed  CAS  Google Scholar 

  110. Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, Lindholm M, Hedtjarn M, Hansen HF, Berger U, Gullans S, Kearney P, Sarnow P, Straarup EM, Kauppinen S (2008) LNA-mediated microRNA silencing in non-human primates. Nature 452(7189):896–899. doi:10.1038/nature06783

    PubMed  CAS  Google Scholar 

  111. Fontana L, Fiori ME, Albini S, Cifaldi L, Giovinazzi S, Forloni M, Boldrini R, Donfrancesco A, Federici V, Giacomini P, Peschle C, Fruci D (2008) Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM. PLoS One 3(5):e2236. doi:10.1371/journal.pone.0002236

    PubMed  Google Scholar 

  112. Care A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, Bang ML, Segnalini P, Gu Y, Dalton ND, Elia L, Latronico MV, Hoydal M, Autore C, Russo MA, Dorn GW 2nd, Ellingsen O, Ruiz-Lozano P, Peterson KL, Croce CM, Peschle C, Condorelli G (2007) MicroRNA-133 controls cardiac hypertrophy. Nat Med 13(5):613–618. doi:10.1038/nm1582

    PubMed  CAS  Google Scholar 

  113. Ibrahim AF, Weirauch U, Thomas M, Grunweller A, Hartmann RK, Aigner A (2011) MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma. Cancer Res 71(15):5214–5224. doi:10.1158/0008-5472.CAN-10-4645

    PubMed  CAS  Google Scholar 

  114. Trang P, Medina PP, Wiggins JF, Ruffino L, Kelnar K, Omotola M, Homer R, Brown D, Bader AG, Weidhaas JB, Slack FJ (2010) Regression of murine lung tumors by the let-7 microRNA. Oncogene 29(11):1580–1587. doi:10.1038/onc.2009.445

    PubMed  CAS  Google Scholar 

  115. Wiggins JF, Ruffino L, Kelnar K, Omotola M, Patrawala L, Brown D, Bader AG (2010) Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res 70(14):5923–5930. doi:10.1158/0008-5472.CAN-10-0655

    PubMed  CAS  Google Scholar 

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Acknowledgments

I am thankful to Dr. Geoffrey Greene, Jessica Bockhorn and Simo Huang in the Greene laboratory, Dr. Yin-yuan Mo, Dr. John Kokontis, and Dr. Richard Hiipakka who read and edited the manuscript. This was supported in part by Department of Defense Breast Cancer Research Program W81XWH-09-1-0331, Paul Calabresi K12 Award 1K12CA139160-02, Chicago Fellows Program at the University of Chicago, and the University of Chicago Clinical and Translational Science Award (UL1 RR024999).

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  1. The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, 60637, USA

    Huiping Liu

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Liu, H. MicroRNAs in breast cancer initiation and progression. Cell. Mol. Life Sci. 69, 3587–3599 (2012). https://doi.org/10.1007/s00018-012-1128-9

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