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MicroRNAs (miRNAs) in cancer invasion and metastasis: therapeutic approaches based on metastasis-related miRNAs

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Abstract

The management of tumor cell invasion and metastasis is instrumental in cancer therapy, since metastases are the prime reason for cancer patient mortality. Various cellular mechanisms and underlying molecular pathways relevant for metastasis have been identified so far, providing a basis for antimetastatic drugs. MicroRNAs (miRNAs) are highly conserved, small noncoding RNA molecules that have been shown to regulate various cellular processes by interfering with protein expression through posttranscriptional repression or mRNA degradation. More importantly, beyond their roles in physiological processes, many miRNAs are aberrantly expressed in various pathologies including cancer and regulate tumor- and metastasis-associated genes. Their pivotal role in metastasis has emerged only recently. After an introduction into the mechanisms of miRNA action, this review article describes the roles of miRNAs in cancer invasion and metastasis. Various miRNAs are discussed with regard to their upstream regulators, downstream target genes, and pro-/antimetastatic effects. A table provides a comprehensive overview of miRNAs that are misregulated/relevant in metastasis and the current knowledge regarding their underlying molecular effects. Furthermore, therapeutic approaches based on miRNAs, either as drugs or as therapeutic targets, are described prior to the discussion of the delivery of miRNA-based therapeutics as novel strategy in antimetastatic treatment.

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References

  1. Hunter KW, Crawford NP, Alsarraj J (2008) Mechanisms of metastasis. Breast Cancer Res 10(Suppl 1):S2

    PubMed  Google Scholar 

  2. Geiger TR, Peeper DS (2009) Metastasis mechanisms. Biochim Biophys Acta 1796:293–308

    PubMed  CAS  Google Scholar 

  3. Nguyen DX, Bos PD, Massague J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9:274–284

    PubMed  CAS  Google Scholar 

  4. Iiizumi M, Liu W, Pai SK, Furuta E, Watabe K (2008) Drug development against metastasis-related genes and their pathways: a rationale for cancer therapy. Biochim Biophys Acta 1786:87–104

    PubMed  CAS  Google Scholar 

  5. Smith SC, Theodorescu D (2009) Learning therapeutic lessons from metastasis suppressor proteins. Nat Rev Cancer 9:253–264

    PubMed  CAS  Google Scholar 

  6. Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572

    PubMed  CAS  Google Scholar 

  7. Amerasekera S, Turner M, Purushotham AD (2004) Paget’s “seed and soil” hypothesis revisited. J BUON 9:465–467

    PubMed  CAS  Google Scholar 

  8. Moustakas A, Heldin CH (2007) Signaling networks guiding epithelial–mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci 98:1512–1520

    PubMed  CAS  Google Scholar 

  9. Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol 7:131–142

    PubMed  CAS  Google Scholar 

  10. Hazan RB, Qiao R, Keren R, Badano I, Suyama K (2004) Cadherin switch in tumor progression. Ann NY Acad Sci 1014:155–163

    PubMed  CAS  Google Scholar 

  11. Peinado H, Olmeda D, Cano A (2007) Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7:415–428

    PubMed  CAS  Google Scholar 

  12. Bracken CP, Gregory PA, Khew-Goodall Y, Goodall GJ (2009) The role of microRNAs in metastasis and epithelial–mesenchymal transition. Cell Mol Life Sci 66:1682–1699

    PubMed  CAS  Google Scholar 

  13. Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269

    PubMed  CAS  Google Scholar 

  14. Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, Wilson M, Wang X, Shelton J, Shingara J et al (2007) The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 67:7713–7722

    PubMed  CAS  Google Scholar 

  15. Wang S, Olson EN (2009) AngiomiRs—key regulators of angiogenesis. Curr Opin Genet Dev 19:205–211

    PubMed  CAS  Google Scholar 

  16. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20

    PubMed  CAS  Google Scholar 

  17. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S et al (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419

    PubMed  CAS  Google Scholar 

  18. Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD (2001) A cellular function for the RNA-interference enzyme dicer in the maturation of the let-7 small temporal RNA. Science 293:834–838

    PubMed  CAS  Google Scholar 

  19. Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, Plasterk RH (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15:2654–2659

    PubMed  CAS  Google Scholar 

  20. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    PubMed  CAS  Google Scholar 

  21. Pillai RS, Bhattacharyya SN, Filipowicz W (2007) Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol 17:118–126

    PubMed  CAS  Google Scholar 

  22. Mathonnet G, Fabian MR, Svitkin YV, Parsyan A, Huck L, Murata T, Biffo S, Merrick WC, Darzynkiewicz E, Pillai RS et al (2007) MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science 317:1764–1767

    PubMed  CAS  Google Scholar 

  23. Shenouda SK, Alahari SK (2009) MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev 28:369–378

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  25. Cho WC (2010) MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol 42:1273–1281

    PubMed  CAS  Google Scholar 

  26. Cho WC (2010) MicroRNAs in cancer—from research to therapy. Biochim Biophys Acta 1805:209–217

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  28. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA et al (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    PubMed  CAS  Google Scholar 

  29. Hui AB, Shi W, Boutros PC, Miller N, Pintilie M, Fyles T, McCready D, Wong D, Gerster K, Waldron L et al (2009) Robust global micro-RNA profiling with formalin-fixed paraffin-embedded breast cancer tissues. Lab Invest 89:597–606

    PubMed  CAS  Google Scholar 

  30. Xi Y, Nakajima G, Gavin E, Morris CG, Kudo K, Hayashi K, Ju J (2007) Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA 13:1668–1674

    PubMed  CAS  Google Scholar 

  31. Vlassov VV, Laktionov PP, Rykova EY (2010) Circulating nucleic acids as a potential source for cancer biomarkers. Curr Mol Med 10:142–165

    PubMed  CAS  Google Scholar 

  32. Kosaka N, Iguchi H, Ochiya T (2010) Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci 101:2087–2092

    PubMed  CAS  Google Scholar 

  33. Corcoran C, Friel AM, Duffy MJ, Crown J, O’Driscoll L (2011) Intracellular and extracellular MicroRNAs in breast cancer. Clin Chem 57:18–32

    Google Scholar 

  34. Bandres E, Agirre X, Bitarte N, Ramirez N, Zarate R, Roman-Gomez J, Prosper F, Garcia-Foncillas J (2009) Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer 125:2737–2743

    PubMed  CAS  Google Scholar 

  35. Spahn M, Kneitz S, Scholz CJ, Stenger N, Rudiger T, Strobel P, Riedmiller H, Kneitz B (2010) Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence. Int J Cancer 127:394–403

    PubMed  CAS  Google Scholar 

  36. Trang P, Weidhaas JB, Slack FJ (2008) MicroRNAs as potential cancer therapeutics. Oncogene 27(Suppl 2):S52–S57

    PubMed  CAS  Google Scholar 

  37. 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 67:11111–11116

    PubMed  CAS  Google Scholar 

  38. Le MT, Teh C, Shyh-Chang N, Xie H, Zhou B, Korzh V, Lodish HF, Lim B (2009) MicroRNA-125b is a novel negative regulator of p53. Genes Dev 23:862–876

    PubMed  CAS  Google Scholar 

  39. Manni I, Artuso S, Careccia S, Rizzo MG, Baserga R, Piaggio G, Sacchi A (2009) The microRNA miR-92 increases proliferation of myeloid cells and by targeting p63 modulates the abundance of its isoforms. FASEB J 23:3957–3966

    PubMed  CAS  Google Scholar 

  40. Scheel AH, Beyer U, Agami R, Dobbelstein M (2009) Immunofluorescence-based screening identifies germ cell associated microRNA 302 as an antagonist to p63 expression. Cell Cycle 8:1426–1432

    PubMed  CAS  Google Scholar 

  41. Papagiannakopoulos T, Shapiro A, Kosik KS (2008) MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res 68:8164–8172

    PubMed  CAS  Google Scholar 

  42. Bussing I, Slack FJ, Grosshans H (2008) let-7 microRNAs in development, stem cells and cancer. Trends Mol Med 14:400–409

    PubMed  Google Scholar 

  43. Wang G, Mao W, Zheng S, Ye J (2009) Epidermal growth factor receptor-regulated miR-125a-5p-a metastatic inhibitor of lung cancer. FEBS J 276:5571–5578

    PubMed  CAS  Google Scholar 

  44. Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder TT, Valastyan S et al (2010) miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol 12:247–256

    PubMed  CAS  Google Scholar 

  45. Sampson VB, Rong NH, Han J, Yang Q, Aris V, Soteropoulos P, Petrelli NJ, Dunn SP, Krueger LJ (2007) MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 67:9762–9770

    PubMed  CAS  Google Scholar 

  46. Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, Dang CV, Thomas-Tikhonenko A, Mendell JT (2008) Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet 40:43–50

    PubMed  CAS  Google Scholar 

  47. Zhang X, Liu S, Hu T, Liu S, He Y, Sun S (2009) Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology 50:490–499

    PubMed  CAS  Google Scholar 

  48. Boominathan L (2010) The tumor suppressors p53, p63, and p73 are regulators of microRNA processing complex. PLoS ONE 5:e10615

    PubMed  Google Scholar 

  49. 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 9:582–589

    PubMed  CAS  Google Scholar 

  50. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, Waldvogel B, Vannier C, Darling D, zur Hausen A et al (2009) The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 11:1487–1495

    PubMed  CAS  Google Scholar 

  51. Selcuklu SD, Donoghue MT, Spillane C (2009) miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans 37:918–925

    PubMed  CAS  Google Scholar 

  52. Hummel R, Hussey DJ, Haier J (2010) MicroRNAs: predictors and modifiers of chemo- and radiotherapy in different tumour types. Eur J Cancer 46:298–311

    PubMed  CAS  Google Scholar 

  53. Boyerinas B, Park SM, Hau A, Murmann AE, Peter ME (2010) The role of let-7 in cell differentiation and cancer. Endocr Relat Cancer 17:F19–F36

    PubMed  CAS  Google Scholar 

  54. Aqeilan RI, Calin GA, Croce CM (2009) miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ 17:215–220

    PubMed  Google Scholar 

  55. Takeshita F, Patrawala L, Osaki M, Takahashi RU, Yamamoto Y, Kosaka N, Kawamata M, Kelnar K, Bader AG, Brown D et al (2010) Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes. Mol Ther 18:181–187

    PubMed  CAS  Google Scholar 

  56. Gregory SA, Morrissey JH, Edgington TS (1989) Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol Cell Biol 9:2752–2755

    PubMed  CAS  Google Scholar 

  57. Krupa A, Jenkins R, Luo DD, Lewis A, Phillips A, Fraser D (2010) Loss of MicroRNA-192 promotes fibrogenesis in diabetic nephropathy. J Am Soc Nephrol 21:438–447

    PubMed  CAS  Google Scholar 

  58. Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J (2009) miR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS ONE 4:e7181

    PubMed  Google Scholar 

  59. Hurteau GJ, Carlson JA, Roos E, Brock GJ (2009) Stable expression of miR-200c alone is sufficient to regulate TCF8 (ZEB1) and restore E-cadherin expression. Cell Cycle 8:2064–2069

    PubMed  CAS  Google Scholar 

  60. Varambally S, Cao Q, Mani RS, Shankar S, Wang X, Ateeq B, Laxman B, Cao X, Jing X, Ramnarayanan K et al (2008) Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322:1695–1699

    PubMed  CAS  Google Scholar 

  61. Min J, Zaslavsky A, Fedele G, McLaughlin SK, Reczek EE, De Raedt T, Guney I, Strochlic DE, Macconaill LE, Beroukhim R et al (2010) An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB. Nat Med 16:286–294

    PubMed  CAS  Google Scholar 

  62. Gibbons DL, Lin W, Creighton CJ, Rizvi ZH, Gregory PA, Goodall GJ, Thilaganathan N, Du L, Zhang Y, Pertsemlidis A et al (2009) Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes Dev 23:2140–2151

    PubMed  CAS  Google Scholar 

  63. Ceppi P, Mudduluru G, Kumarswamy R, Rapa I, Scagliotti GV, Papotti M, Allgayer H (2010) Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer. Mol Cancer Res 8:1207–1216

    PubMed  CAS  Google Scholar 

  64. Valastyan S, Chang A, Benaich N, Reinhardt F, Weinberg RA (2010) Concurrent suppression of integrin alpha5, radixin, and RhoA phenocopies the effects of miR-31 on metastasis. Cancer Res 70:5147–5154

    PubMed  CAS  Google Scholar 

  65. Valastyan S, Benaich N, Chang A, Reinhardt F, Weinberg RA (2009) Concomitant suppression of three target genes can explain the impact of a microRNA on metastasis. Genes Dev 23:2592–2597

    PubMed  CAS  Google Scholar 

  66. 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 137:1032–1046

    PubMed  CAS  Google Scholar 

  67. Esquela-Kerscher A, Trang P, Wiggins JF, Patrawala L, Cheng A, Ford L, Weidhaas JB, Brown D, Bader AG, Slack FJ (2008) The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle 7:759–764

    PubMed  CAS  Google Scholar 

  68. Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR et al (2009) Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137:1005–1017

    PubMed  CAS  Google Scholar 

  69. 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 70:5923–5930

    PubMed  CAS  Google Scholar 

  70. Trang P, Medina PP, Wiggins JF, Ruffino L, Kelnar K, Omotola M, Homer R, Brown D, Bader AG, Weidhaas JB et al (2010) Regression of murine lung tumors by the let-7 microRNA. Oncogene 29:1580–1587

    PubMed  CAS  Google Scholar 

  71. Akao Y, Nakagawa Y, Hirata I, Iio A, Itoh T, Kojima K, Nakashima R, Kitade Y, Naoe T (2010) Role of anti-oncomirs miR-143 and -145 in human colorectal tumors. Cancer Gene Ther 17:398–408

    PubMed  CAS  Google Scholar 

  72. Gleave ME, Monia BP (2005) Antisense therapy for cancer. Nat Rev Cancer 5:468–479

    PubMed  CAS  Google Scholar 

  73. Aigner A (2007) Applications of RNA interference: current state and prospects for siRNA-based strategies in vivo. Appl Microbiol Biotechnol 76:9–21

    PubMed  CAS  Google Scholar 

  74. Bumcrot D, Manoharan M, Koteliansky V, Sah DW (2006) RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol 2:711–719

    PubMed  CAS  Google Scholar 

  75. Chan CW, Khachigian LM (2009) DNAzymes and their therapeutic possibilities. Intern Med J 39:249–251

    PubMed  CAS  Google Scholar 

  76. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, Watts L, Booten SL, Graham M, McKay R et al (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 3:87–98

    PubMed  CAS  Google Scholar 

  77. Vester B, Wengel J (2004) LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA. Biochemistry 43:13233–13241

    PubMed  CAS  Google Scholar 

  78. Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033

    PubMed  CAS  Google Scholar 

  79. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY (2007) miR-21-mediated tumor growth. Oncogene 26:2799–2803

    PubMed  CAS  Google Scholar 

  80. Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, Lindholm M, Hedtjarn M, Hansen HF, Berger U et al (2008) LNA-mediated microRNA silencing in non-human primates. Nature 452:896–899

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  82. Gumireddy K, Young DD, Xiong X, Hogenesch JB, Huang Q, Deiters A (2008) Small-molecule inhibitors of microRNA miR-21 function. Angew Chem Int Ed Engl 47:7482–7484

    PubMed  CAS  Google Scholar 

  83. Gentner B, Schira G, Giustacchini A, Amendola M, Brown BD, Ponzoni M, Naldini L (2009) Stable knockdown of microRNA in vivo by lentiviral vectors. Nat Methods 6:63–66

    PubMed  CAS  Google Scholar 

  84. Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, Kirak O, Brummelkamp TR, Fleming MD, Camargo FD (2008) Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 451:1125–1129

    PubMed  CAS  Google Scholar 

  85. 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 28:341–347

    PubMed  CAS  Google Scholar 

  86. Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA, Jacks T (2008) Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci USA 105:3903–3908

    PubMed  CAS  Google Scholar 

  87. Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D’Urso L, Pagliuca A, Biffoni M, Labbaye C et al (2008) The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14:1271–1277

    PubMed  CAS  Google Scholar 

  88. Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, Jiang J, Schmittgen TD, Patel T (2006) Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 130:2113–2129

    PubMed  CAS  Google Scholar 

  89. Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK (2009) MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol Cancer Ther 8:1055–1066

    PubMed  CAS  Google Scholar 

  90. Itaka K, Kataoka K (2009) Recent development of nonviral gene delivery systems with virus-like structures and mechanisms. Eur J Pharm Biopharm 71:475–483

    PubMed  CAS  Google Scholar 

  91. Aigner A (2008) Cellular delivery in vivo of siRNA-based therapeutics. Curr Pharm Des 14:3603–3619

    PubMed  CAS  Google Scholar 

  92. Aigner A (2007) Nonviral in vivo delivery of therapeutic small interfering RNAs. Curr Opin Mol Ther 9:345–352

    PubMed  CAS  Google Scholar 

  93. Reddy SD, Ohshiro K, Rayala SK, Kumar R (2008) MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions. Cancer Res 68:8195–8200

    PubMed  CAS  Google Scholar 

  94. Veerla S, Lindgren D, Kvist A, Frigyesi A, Staaf J, Persson H, Liedberg F, Chebil G, Gudjonsson S, Borg A et al (2009) MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer 124:2236–2242

    PubMed  CAS  Google Scholar 

  95. Yu Z, Willmarth NE, Zhou J, Katiyar S, Wang M, Liu Y, McCue PA, Quong AA, Lisanti MP, Pestell RG (2010) microRNA 17/20 inhibits cellular invasion and tumor metastasis in breast cancer by heterotypic signaling. Proc Natl Acad Sci U S A 107:8231–8236

    PubMed  CAS  Google Scholar 

  96. Li J, Liang S, Yu H, Zhang J, Ma D, Lu X (2010) An inhibitory effect of miR-22 on cell migration and invasion in ovarian cancer. Gynecol Oncol 119:543–548

    PubMed  CAS  Google Scholar 

  97. Salvi A, Sabelli C, Moncini S, Venturin M, Arici B, Riva P, Portolani N, Giulini SM, De Petro G, Barlati S (2009) MicroRNA-23b mediates urokinase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cells. FEBS J 276:2966–2982

    PubMed  CAS  Google Scholar 

  98. Steele R, Mott JL, Ray RB (2010) MBP-1 upregulates miR-29b that represses Mcl-1, collagens, and matrix-metalloproteinase-2 in prostate cancer cells. Genes Cancer 1:381–387

    PubMed  CAS  Google Scholar 

  99. Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng YJ, Chen CJ, Hildesheim A, Sugden B, Ahlquist P (2008) MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci USA 105:5874–5878

    PubMed  CAS  Google Scholar 

  100. 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 29:4194–4204

    PubMed  CAS  Google Scholar 

  101. Li N, Fu H, Tie Y, Hu Z, Kong W, Wu Y, Zheng X (2009) miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett 275:44–53

    PubMed  CAS  Google Scholar 

  102. Slaby O, Jancovicova J, Lakomy R, Svoboda M, Poprach A, Fabian P, Kren L, Michalek J, Vyzula R (2010) Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy. J Exp Clin Cancer Res 29:90

    PubMed  Google Scholar 

  103. Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS (2009) Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene 28:3526–3536

    PubMed  CAS  Google Scholar 

  104. Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW, Chen CM, Lin CD, Liao YL, Wang JL, Chau YP et al (2009) MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology 49:1571–1582

    PubMed  CAS  Google Scholar 

  105. Liang L, Wong CM, Ying Q, Fan DN, Huang S, Ding J, Yao J, Yan M, Li J, Yao M et al (2010) MicroRNA-125b suppressed human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2. Hepatology 52:1731–1740

    PubMed  CAS  Google Scholar 

  106. Crawford M, Brawner E, Batte K, Yu L, Hunter MG, Otterson GA, Nuovo G, Marsh CB, Nana-Sinkam SP (2008) MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines. Biochem Biophys Res Commun 373:607–612

    PubMed  CAS  Google Scholar 

  107. Feng R, Chen X, Yu Y, Su L, Yu B, Li J, Cai Q, Yan M, Liu B, Zhu Z (2010) miR-126 functions as a tumour suppressor in human gastric cancer. Cancer Lett 298:50–63

    PubMed  CAS  Google Scholar 

  108. 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 451:147–152

    PubMed  CAS  Google Scholar 

  109. Su X, Chakravarti D, Cho MS, Liu L, Gi YJ, Lin YL, Leung ML, El-Naggar A, Creighton CJ, Suraokar MB et al (2010) TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature 467:986–990

    PubMed  CAS  Google Scholar 

  110. Liu X, Jiang L, Wang A, Yu J, Shi F, Zhou X (2009) MicroRNA-138 suppresses invasion and promotes apoptosis in head and neck squamous cell carcinoma cell lines. Cancer Lett 286:217–222

    PubMed  CAS  Google Scholar 

  111. Wong CC, Wong CM, Tung EK, Au SL, Lee JM, Poon RT, Man K, Ng IO (2010) The MicroRNA MiR-139 suppresses metastasis and progression of hepatocellular carcinoma by down-regulating Rho-kinase 2. Gastroenterology 140:322–331

    PubMed  Google Scholar 

  112. Sachdeva M, Mo YY (2010) miR-145-mediated suppression of cell growth, invasion and metastasis. Am J Transl Res 2:170–180

    PubMed  CAS  Google Scholar 

  113. Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR (2009) Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res 69:1279–1283

    PubMed  CAS  Google Scholar 

  114. Edmonds MD, Hurst DR, Vaidya KS, Stafford LJ, Chen D, Welch DR (2009) Breast cancer metastasis suppressor 1 coordinately regulates metastasis-associated microRNA expression. Int J Cancer 125:1778–1785

    PubMed  CAS  Google Scholar 

  115. Li Y, Vandenboom TG 2nd, Wang Z, Kong D, Ali S, Philip PA, Sarkar FH (2010) miR-146a suppresses invasion of pancreatic cancer cells. Cancer Res 70:1486–1495

    PubMed  CAS  Google Scholar 

  116. Xia H, Qi Y, Ng SS, Chen X, Li D, Chen S, Ge R, Jiang S, Li G, Chen Y et al (2009) microRNA-146b inhibits glioma cell migration and invasion by targeting MMPs. Brain Res 1269:158–165

    PubMed  CAS  Google Scholar 

  117. Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC (2008) Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 27:5643–5647

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  120. 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 28:3937–3948

    PubMed  CAS  Google Scholar 

  121. Meng Z, Fu X, Chen X, Zeng S, Tian Y, Jove R, Xu R, Huang W (2010) miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice. Hepatology 52:2148–2157

    PubMed  CAS  Google Scholar 

  122. Lee Y, Yang X, Huang Y, Fan H, Zhang Q, Wu Y, Li J, Hasina R, Cheng C, Lingen MW et al (2010) Network modeling identifies molecular functions targeted by miR-204 to suppress head and neck tumor metastasis. PLoS Comput Biol 6:e1000730

    PubMed  Google Scholar 

  123. Neely LA, Rieger-Christ KM, Neto BS, Eroshkin A, Garver J, Patel S, Phung NA, McLaughlin S, Libertino JA, Whitney D et al (2008) A microRNA expression ratio defining the invasive phenotype in bladder tumors. Urol Oncol 28:39–48

    PubMed  Google Scholar 

  124. 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

    PubMed  CAS  Google Scholar 

  125. Paterson EL, Kolesnikoff N, Gregory PA, Bert AG, Khew-Goodall Y, Goodall GJ (2008) The microRNA-200 family regulates epithelial to mesenchymal transition. ScientificWorldJournal 8:901–904

    PubMed  CAS  Google Scholar 

  126. Song H, Bu G (2009) MicroRNA-205 inhibits tumor cell migration through down-regulating the expression of the LDL receptor-related protein 1. Biochem Biophys Res Commun 388:400–405

    PubMed  CAS  Google Scholar 

  127. Wu H, Zhu S, Mo YY (2009) Suppression of cell growth and invasion by miR-205 in breast cancer. Cell Res 19:439–448

    PubMed  CAS  Google Scholar 

  128. Song G, Zhang Y, Wang L (2009) MicroRNA-206 targets notch3, activates apoptosis, and inhibits tumor cell migration and focus formation. J Biol Chem 284:31921–31927

    PubMed  CAS  Google Scholar 

  129. Wang X, Ling C, Bai Y, Zhao J (2010) MicroRNA-206 is associated with invasion and metastasis of lung cancer. Anat Rec (Hoboken) 294:88–92

    Google Scholar 

  130. Mazar J, Deyoung K, Khaitan D, Meister E, Almodovar A, Goydos J, Ray A, Perera RJ (2010) The regulation of miRNA-211 expression and its role in melanoma cell invasiveness. PLoS ONE 5:e13779

    PubMed  Google Scholar 

  131. Tie J, Pan Y, Zhao L, Wu K, Liu J, Sun S, Guo X, Wang B, Gang Y, Zhang Y et al (2010) MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. PLoS Genet 6:e1000879

    PubMed  Google Scholar 

  132. Liu X, Yu J, Jiang L, Wang A, Shi F, Ye H, Zhou X (2009) MicroRNA-222 regulates cell invasion by targeting matrix metalloproteinase 1 (MMP1) and manganese superoxide dismutase 2 (SOD2) in tongue squamous cell carcinoma cell lines. Cancer Genomics Proteomics 6:131–139

    PubMed  CAS  Google Scholar 

  133. Huang XH, Wang Q, Chen JS, Fu XH, Chen XL, Chen LZ, Li W, Bi J, Zhang LJ, Fu Q et al (2009) Bead-based microarray analysis of microRNA expression in hepatocellular carcinoma: miR-338 is downregulated. Hepatol Res 39:786–794

    PubMed  CAS  Google Scholar 

  134. Wu ZS, Wu Q, Wang CQ, Wang XN, Wang Y, Zhao JJ, Mao SS, Zhang GH, Zhang N, Xu XC (2010) MiR-339-5p inhibits breast cancer cell migration and invasion in vitro and may be a potential biomarker for breast cancer prognosis. BMC Cancer 10:542

    PubMed  Google Scholar 

  135. Dangi-Garimella S, Yun J, Eves EM, Newman M, Erkeland SJ, Hammond SM, Minn AJ, Rosner MR (2009) Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. EMBO J 28:347–358

    PubMed  CAS  Google Scholar 

  136. Mayr C, Hemann MT, Bartel DP (2007) Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 315:1576–1579

    PubMed  CAS  Google Scholar 

  137. Ji J, Zhao L, Budhu A, Forgues M, Jia HL, Qin LX, Ye QH, Yu J, Shi X, Tang ZY et al (2010) Let-7g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. J Hepatol 52:690–697

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  139. Moriarty CH, Pursell B, Mercurio AM (2010) miR-10b targets Tiam1: implications for Rac activation and carcinoma migration. J Biol Chem 285:20541–20546

    PubMed  CAS  Google Scholar 

  140. Li G, Wu Z, Peng Y, Liu X, Lu J, Wang L, Pan Q, He ML, Li XP (2010) MicroRNA-10b induced by Epstein–Barr virus-encoded latent membrane protein-1 promotes the metastasis of human nasopharyngeal carcinoma cells. Cancer Lett 299:29–36

    PubMed  CAS  Google Scholar 

  141. Jiang L, Huang Q, Zhang S, Zhang Q, Chang J, Qiu X, Wang E (2010) Hsa-miR-125a-3p and hsa-miR-125a-5p are downregulated in non-small cell lung cancer and have inverse effects on invasion and migration of lung cancer cells. BMC Cancer 10:318

    PubMed  Google Scholar 

  142. Cowden Dahl KD, Dahl R, Kruichak JN, Hudson LG (2009) The epidermal growth factor receptor responsive miR-125a represses mesenchymal morphology in ovarian cancer cells. Neoplasia 11:1208–1215

    PubMed  CAS  Google Scholar 

  143. Sossey-Alaoui K, Bialkowska K, Plow EF (2009) The miR200 family of microRNAs regulates WAVE3-dependent cancer cell invasion. J Biol Chem 284:33019–33029

    PubMed  CAS  Google Scholar 

  144. Mees ST, Mardin WA, Wendel C, Baeumer N, Willscher E, Senninger N, Schleicher C, Colombo-Benkmann M, Haier J (2010) EP300—a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas. Int J Cancer 126:114–124

    PubMed  CAS  Google Scholar 

  145. Reddy SD, Pakala SB, Ohshiro K, Rayala SK, Kumar R (2009) MicroRNA-661, a c/EBPalpha target, inhibits metastatic tumor antigen 1 and regulates its functions. Cancer Res 69:5639–5642

    PubMed  CAS  Google Scholar 

  146. Vetter G, Saumet A, Moes M, Vallar L, Le Bechec A, Laurini C, Sabbah M, Arar K, Theillet C, Lecellier CH et al (2010) miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers. Oncogene 29:4436–4448

    PubMed  CAS  Google Scholar 

  147. Hao-Xiang T, Qian W, Lian-Zhou C, Xiao-Hui H, Jin-Song C, Xin-Hui F, Liang-Qi C, Xi-Ling C, Wen L, Long-Juan Z (2009) MicroRNA-9 reduces cell invasion and E-cadherin secretion in SK-Hep-1 cell. Med Oncol 27:654–660

    Google Scholar 

  148. Nass D, Rosenwald S, Meiri E, Gilad S, Tabibian-Keissar H, Schlosberg A, Kuker H, Sion-Vardy N, Tobar A, Kharenko O et al (2009) MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can be used to differentiate primary from metastatic brain tumors. Brain Pathol 19:375–383

    PubMed  CAS  Google Scholar 

  149. Weiss FU, Marques IJ, Woltering JM, Vlecken DH, Aghdassi A, Partecke LI, Heidecke CD, Lerch MM, Bagowski CP (2009) Retinoic acid receptor antagonists inhibit miR-10a expression and block metastatic behavior of pancreatic cancer. Gastroenterology 137(2136–45):e1–e7

    PubMed  Google Scholar 

  150. Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT et al (2006) Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet 38:1060–1065

    PubMed  CAS  Google Scholar 

  151. Liu S, Goldstein RH, Scepansky EM, Rosenblatt M (2009) Inhibition of rho-associated kinase signaling prevents breast cancer metastasis to human bone. Cancer Res 69:8742–8751

    PubMed  CAS  Google Scholar 

  152. 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 27:2128–2136

    PubMed  CAS  Google Scholar 

  153. Davis BN, Hilyard AC, Lagna G, Hata A (2008) SMAD proteins control DROSHA-mediated microRNA maturation. Nature 454:56–61

    PubMed  CAS  Google Scholar 

  154. Du J, Yang S, An D, Hu F, Yuan W, Zhai C, Zhu T (2009) BMP-6 inhibits microRNA-21 expression in breast cancer through repressing deltaEF1 and AP-1. Cell Res 19:487–496

    PubMed  CAS  Google Scholar 

  155. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH (2008) Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 283:1026–1033

    PubMed  CAS  Google Scholar 

  156. Fujita S, Ito T, Mizutani T, Minoguchi S, Yamamichi N, Sakurai K, Iba H (2008) miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism. J Mol Biol 378:492–504

    PubMed  CAS  Google Scholar 

  157. 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 28:5369–5380

    PubMed  CAS  Google Scholar 

  158. Li T, Li D, Sha J, Sun P, Huang Y (2009) MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun 383:280–285

    PubMed  CAS  Google Scholar 

  159. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133:647–658

    PubMed  CAS  Google Scholar 

  160. Sayed D, Rane S, Lypowy J, He M, Chen IY, Vashistha H, Yan L, Malhotra A, Vatner D, Abdellatif M (2008) MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol Biol Cell 19:3272–3282

    PubMed  CAS  Google Scholar 

  161. Selaru FM, Olaru AV, Kan T, David S, Cheng Y, Mori Y, Yang J, Paun B, Jin Z, Agarwal R et al (2009) MicroRNA-21 is overexpressed in human cholangiocarcinoma and regulates programmed cell death 4 and tissue inhibitor of metalloproteinase 3. Hepatology 49:1595–1601

    PubMed  CAS  Google Scholar 

  162. Talotta F, Cimmino A, Matarazzo MR, Casalino L, De Vita G, D’Esposito M, Di Lauro R, Verde P (2009) An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation. Oncogene 28:73–84

    PubMed  CAS  Google Scholar 

  163. 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 18:350–359

    PubMed  CAS  Google Scholar 

  164. Zhu S, Si ML, Wu H, Mo YY (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282:14328–14336

    PubMed  CAS  Google Scholar 

  165. Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK et al (2008) MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. Jama 299:425–436

    PubMed  CAS  Google Scholar 

  166. Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, Nenutil R, Vyzula R (2007) Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology 72:397–402

    PubMed  CAS  Google Scholar 

  167. Nam EJ, Yoon H, Kim SW, Kim H, Kim YT, Kim JH, Kim JW, Kim S (2008) MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res 14:2690–2695

    PubMed  CAS  Google Scholar 

  168. Song B, Wang C, Liu J, Wang X, Lv L, Wei L, Xie L, Zheng Y, Song X (2010) MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression. J Exp Clin Cancer Res 29:29

    PubMed  CAS  Google Scholar 

  169. Zhang JG, Wang JJ, Zhao F, Liu Q, Jiang K, Yang GH (2010) MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin Chim Acta 411:846–852

    PubMed  CAS  Google Scholar 

  170. Huang TH, Wu F, Loeb GB, Hsu R, Heidersbach A, Brincat A, Horiuchi D, Lebbink RJ, Mo YY, Goga A et al (2009) Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion. J Biol Chem 284:18515–18524

    PubMed  CAS  Google Scholar 

  171. Hiyoshi Y, Kamohara H, Karashima R, Sato N, Imamura Y, Nagai Y, Yoshida N, Toyama E, Hayashi N, Watanabe M et al (2009) MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. Clin Cancer Res 15:1915–1922

    PubMed  CAS  Google Scholar 

  172. Katada T, Ishiguro H, Kuwabara Y, Kimura M, Mitui A, Mori Y, Ogawa R, Harata K, Fujii Y (2009) microRNA expression profile in undifferentiated gastric cancer. Int J Oncol 34:537–542

    PubMed  CAS  Google Scholar 

  173. Wang Y, Rathinam R, Walch A, Alahari SK (2009) ST14 (suppression of tumorigenicity 14) gene is a target for miR-27b, and the inhibitory effect of ST14 on cell growth is independent of miR-27b regulation. J Biol Chem 284:23094–23106

    PubMed  CAS  Google Scholar 

  174. Gebeshuber CA, Zatloukal K, Martinez J (2009) miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Rep 10:400–405

    PubMed  CAS  Google Scholar 

  175. Yao J, Liang L, Huang S, Ding J, Tan N, Zhao Y, Yan M, Ge C, Zhang Z, Chen T et al (2010) MicroRNA-30d promotes tumor invasion and metastasis by targeting Galphai2 in hepatocellular carcinoma. Hepatology 51:846–856

    PubMed  CAS  Google Scholar 

  176. Li X, Zhang Y, Shi Y, Dong G, Liang J, Han Y, Wang X, Zhao Q, Ding J, Wu K et al (2010) MicroRNA-107, an oncogene MicroRNA that regulates tumor invasion and metastasis by targeting DICER1 in gastric cancer: MiR-107 promotes gastric cancer invasion and metastasis. J Cell Mol Med. doi:10.1111/j.1582-4934.2010.01194.x

  177. Chen Y, Gorski DH (2008) Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood 111:1217–1226

    PubMed  CAS  Google Scholar 

  178. Ding J, Huang S, Wu S, Zhao Y, Liang L, Yan M, Ge C, Yao J, Chen T, Wan D et al (2010) Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nat Cell Biol 12:390–399

    PubMed  CAS  Google Scholar 

  179. Kong W, Yang H, He L, Zhao JJ, Coppola D, Dalton WS, Cheng JQ (2008) MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol 28:6773–6784

    PubMed  CAS  Google Scholar 

  180. Segura MF, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez-Diaz S, Zakrzewski J, Blochin E, Rose A, Bogunovic D et al (2009) Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci USA 106:1814–1819

    PubMed  CAS  Google Scholar 

  181. Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, Klijn JG, Wiemer EA, Martens JW (2008) Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci USA 105:13021–13026

    PubMed  CAS  Google Scholar 

  182. Mees ST, Mardin WA, Sielker S, Willscher E, Senninger N, Schleicher C, Colombo-Benkmann M, Haier J (2009) Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas. Ann Surg Oncol 16:2339–2350

    PubMed  Google Scholar 

  183. Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, Egan DA, Li A, Huang G, Klein-Szanto AJ et al (2008) The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 10:202–210

    PubMed  CAS  Google Scholar 

  184. Lee DY, Deng Z, Wang CH, Yang BB (2007) MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proc Natl Acad Sci USA 104:20350–20355

    PubMed  CAS  Google Scholar 

  185. Su JL, Chen PB, Chen YH, Chen SC, Chang YW, Jan YH, Cheng X, Hsiao M, Hung MC (2010) Downregulation of microRNA miR-520h by E1A contributes to anticancer activity. Cancer Res 70:5096–5108

    PubMed  CAS  Google Scholar 

  186. Kitago M, Martinez SR, Nakamura T, Sim MS, Hoon DS (2009) Regulation of RUNX3 tumor suppressor gene expression in cutaneous melanoma. Clin Cancer Res 15:2988–2994

    PubMed  CAS  Google Scholar 

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Acknowledgments

The author’s work on miRNAs is supported by grants from the Deutsche Forschungsgemeinschaft (German Research Foundation; Forschergruppe “Nanohale” AI 24/6-1 and DFG single grant AI 24/9-1) and the Deutsche Krebshilfe (German Cancer Aid, grant 106992). The author is grateful to Dr. Tim Plant for critically reading the manuscript.

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  1. Institute of Pharmacology, Faculty of Medicine, Philipps-University Marburg, Karl-von-Frisch-Strasse 1, 35032, Marburg, Germany

    Achim Aigner

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Aigner, A. MicroRNAs (miRNAs) in cancer invasion and metastasis: therapeutic approaches based on metastasis-related miRNAs. J Mol Med 89, 445–457 (2011). https://doi.org/10.1007/s00109-010-0716-0

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