Cellular and Molecular Life Sciences

, Volume 73, Issue 13, pp 2531–2542 | Cite as

Dissecting the role of microRNAs in prostate cancer metastasis: implications for the design of novel therapeutic approaches

  • Valentina Doldi
  • Marzia Pennati
  • Barbara Forte
  • Paolo Gandellini
  • Nadia Zaffaroni


Metastatic prostate cancer is a lethal disease that remains incurable despite the recent approval of new drugs, thus making the development of alternative treatment approaches urgently needed. A more precise understanding of the molecular mechanisms underlying prostate cancer dissemination could lead to the identification of novel therapeutic targets for the design of efficient anti-metastatic strategies. MicroRNA (miRNAs) are endogenous, small non-coding RNA molecules acting as key regulators of gene expression at post-transcriptional level. It has been clearly established that altered miRNA expression is a common hallmark of cancer. In addition, emerging evidence suggests their direct involvement in the metastatic cascade. In this review, we present a comprehensive overview of the data generated in experimental tumor models indicating that specific miRNAs may impinge on the different stages of prostate cancer metastasis, including (i) the regulation of epithelial-to-mesenchymal transition and cell migration/invasion, (ii) the interplay between cancer cells and the surrounding stroma, (iii) the control of angiogenesis, (iv) the regulation of anoikis, and (v) the colonization of distant organs. Moreover, we show preliminary evidence of the clinical relevance of some of these miRNAs, in terms of association with tumor aggressiveness/dissemination and clinical outcome, as emerged from translation studies carried out in prostate cancer patient cohorts. We also discuss the potential and the current limitations of manipulating metastasis-related miRNAs, by mimicking or inhibiting them, as a strategy for the development of novel therapeutic approaches for the advanced disease.


MicroRNA Metastasis Prostate cancer Therapeutic targets 



The work in the authors’ laboratory was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), Projects #11542 (PG) and #12162 (NZ), and the I. Monzino Foundation (NZ).


  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2014) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. doi: 10.1002/ijc.29210 CrossRefPubMedGoogle Scholar
  2. 2.
    Schröder FH, Hugosson J, Roobol MJ, Tammela TL et al (2014) ERSPC Investigators. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 384(9959):2027–2035. doi: 10.1016/S0140-6736(14)60525-0 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bangma CH, Valdagni R, Carroll PR, van Poppel H, Klotz L, Hugosson J (2015) Active surveillance for low-risk prostate cancer: developments to date. Eur Urol 67(4):646–648. doi: 10.1016/j.eururo.2014.11.004 CrossRefPubMedGoogle Scholar
  4. 4.
    Hathaway AR, Baker MK, Sonpavde G (2015) Emerging agents for the therapy of advanced prostate cancer. Future Oncol 11(20):2775–2787. doi: 10.2217/fon.15.224 CrossRefPubMedGoogle Scholar
  5. 5.
    Vanharanta S, Massagué J (2013) Origins of metastatic traits. Cancer Cell 24(4):410–421. doi: 10.1016/j.ccr.2013.09.007 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147(2):275–292. doi: 10.1016/j.cell.2011.09.024 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Mittempergher L, Saghatchian M, Wolf DM, Michiels S, Canisius S, Dessen P, Delaloge S, Lazar V, Benz SC, Tursz T, Bernards R, van’t Veer LJ (2013) A gene signature for late distant metastasis in breast cancer identifies a potential mechanism of late recurrences. Mol Oncol 7(5):987–999. doi: 10.1016/j.molonc.2013.07.006 CrossRefPubMedGoogle Scholar
  8. 8.
    Tlsty TD, Coussens LM (2006) Tumor stroma and regulation of cancer development. Annu Rev Pathol 1:119–150CrossRefPubMedGoogle Scholar
  9. 9.
    Fenderico N, Casamichele A, Profumo V, Zaffaroni N, Gandellini P (2013) MicroRNA-mediated control of prostate cancer metastasis: implications for the identification of novel biomarkers and therapeutic targets. Curr Med Chem 20(12):1566–1584CrossRefPubMedGoogle Scholar
  10. 10.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. doi: 10.1016/j.cell.2009.01.00219167326 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R (2008) MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci USA 105(5):1608–1613. doi: 10.1073/pnas.0707594105 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Jansson MD, Lund AH (2012) MicroRNA and cancer. Mol Oncol 6(6):590–610. doi: 10.1016/j.molonc.2012.09.006 CrossRefPubMedGoogle Scholar
  13. 13.
    Acloque H, Thiery JP, Nieto MA (2008) The physiology and pathology of the EMT. Meeting on the epithelial–mesenchymal transition. EMBO Rep 9(4):322–326. doi: 10.1038/embor.2008.30 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Miska EA (2008) MicroRNAs—keeping cells in formation. Nat Cell Biol 10(5):501–502. doi: 10.1038/ncb0508-501 CrossRefPubMedGoogle Scholar
  15. 15.
    Gandellini P, Folini M, Longoni N, Pennati M, Binda M, Colecchia M, Salvioni R, Supino R, Moretti R, Limonta P, Valdagni R, Daidone MG, Zaffaroni N (2009) miR-205 exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase Cepsilon. Cancer Res 69(6):2287–2295. doi: 10.1158/0008-5472.CAN-08-2894 CrossRefPubMedGoogle Scholar
  16. 16.
    Nishikawa R, Goto Y, Kurozumi A, Matsushita R, Enokida H, Kojima S, Naya Y, Nakagawa M, Ichikawa T, Seki N (2015) MicroRNA-205 inhibits cancer cell migration and invasion via modulation of centromere protein F regulating pathways in prostate cancer. Int J Urol 22(9):867–877. doi: 10.1111/iju.12829 CrossRefPubMedGoogle Scholar
  17. 17.
    Ru P, Steele R, Newhall P, Phillips NJ, Toth K, Ray RB (2012) miRNA-29b suppresses prostate cancer metastasis by regulating epithelial–mesenchymal transition signaling. Mol Cancer Ther 11(5):1166–1173. doi: 10.1158/1535-7163.MCT-12-0100 CrossRefPubMedGoogle Scholar
  18. 18.
    Liu YN, Yin JJ, Abou-Kheir W, Hynes PG, Casey OM, Fang L, Yi M, Stephens RM, Seng V, Sheppard-Tillman H, Martin P, Kelly K (2013) MiR-1 and miR-200 inhibit EMT via Slug-dependent and tumorigenesis via Slug-independent mechanisms. Oncogene 32(3):296–306. doi: 10.1038/onc.2012.58 CrossRefPubMedGoogle Scholar
  19. 19.
    Viticchiè G, Lena AM, Latina A, Formosa A, Gregersen LH, Lund AH, Bernardini S, Mauriello A, Miano R, Spagnoli LG, Knight RA, Candi E, Melino G (2011) MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell Cycle 10(7):1121–1131CrossRefPubMedGoogle Scholar
  20. 20.
    Qu Y, Li WC, Hellem MR, Rostad K, Popa M, McCormack E, Oyan AM, Kalland KH, Ke XS (2013) MiR-182 and miR-203 induce mesenchymal to epithelial transition and self-sufficiency of growth signals via repressing SNAI2 in prostate cells. Int J Cancer 133(3):544–555. doi: 10.1002/ijc.28056 CrossRefPubMedGoogle Scholar
  21. 21.
    Majid S, Dar AA, Saini S, Shahryari V, Arora S, Zaman MS, Chang I, Yamamura S, Tanaka Y, Chiyomaru T, Deng G, Dahiya R (2013) miRNA-34b inhibits prostate cancer through demethylation, active chromatin modifications, and AKT pathways. Clin Cancer Res 19(1):73–84. doi: 10.1158/1078-0432.CCR-12-2952 CrossRefPubMedGoogle Scholar
  22. 22.
    Ren D, Wang M, Guo W, Huang S, Wang Z, Zhao X, Du H, Song L, Peng X (2014) Double-negative feedback loop between ZEB2 and miR-145 regulates epithelial–mesenchymal transition and stem cell properties in prostate cancer cells. Cell Tissue Res 358(3):763–778. doi: 10.1007/s00441-014-2001-y CrossRefPubMedGoogle Scholar
  23. 23.
    Wang L, Song G, Tan W, Qi M, Zhang L, Chan J, Yu J, Han J, Han B (2015) miR-573 inhibits prostate cancer metastasis by regulating epithelial–mesenchymal transition. Oncotarget 6(34):35978–35990. doi: 10.18632/oncotarget.5427 PubMedPubMedCentralGoogle Scholar
  24. 24.
    Kurozumi A, Goto Y, Matsushita R, Fukumoto I, Kato M, Nishikawa R, Sakamoto S, Enokida H, Nakagawa M, Ichikawa T, Seki N (2015) Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer. Cancer Sci. doi: 10.1111/cas.12842 PubMedPubMedCentralGoogle Scholar
  25. 25.
    Shirakihara T, Kawasaki T, Fukagawa A, Semba K, Sakai R, Miyazono K, Miyazawa K, Saitoh M (2013) Identification of integrin α3 as a molecular marker of cells undergoing epithelial–mesenchymal transition and of cancer cells with aggressive phenotypes. Cancer Sci 104(9):1189–1197. doi: 10.1111/cas.12220 CrossRefPubMedGoogle Scholar
  26. 26.
    Yang J, Hou Y, Zhou M, Wen S, Zhou J, Xu L, Tang X, Du YE, Hu P, Liu M (2015) Twist induces epithelial–mesenchymal transition and cell motility in breast cancer via ITGB1-FAK/ILK signaling axis and its associated downstream network. Int J Biochem Cell Biol 71:62–71. doi: 10.1016/j.biocel.2015.12.004 CrossRefPubMedGoogle Scholar
  27. 27.
    Heasman SJ, Ridley AJ (2008) Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol 9(9):690–701. doi: 10.1038/nrm2476 CrossRefPubMedGoogle Scholar
  28. 28.
    Lin SL, Chiang A, Chang D, Ying SY (2008) Loss of mir-146a function in hormone-refractory prostate cancer. RNA 14(3):417–424. doi: 10.1261/rna.874808 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Moser B, Wolf M, Walz A, Loetscher P (2004) Chemokines: multiple levels of leukocyte migration control. Trends Immunol 25(2):75–84CrossRefPubMedGoogle Scholar
  30. 30.
    Dillenburg-Pilla P, Patel V, Mikelis CM, Zárate-Bladés CR, Doçi CL, Amornphimoltham P, Wang Z, Martin D, Leelahavanichkul K, Dorsam RT, Masedunskas A, Weigert R, Molinolo AA, Gutkind JS (2015) SDF-1/CXCL12 induces directional cell migration and spontaneous metastasis via a CXCR4/Gαi/mTORC1 axis. FASEB J 29(3):1056–1068. doi: 10.1096/fj.14-260083 CrossRefPubMedGoogle Scholar
  31. 31.
    Ma N, Pang H, Shen W, Zhang F, Cui Z, Wang J, Wang J, Liu L, Zhang H (2015) Downregulation of CXCR4 by SDF-KDEL in SBC-5 cells inhibits their migration in vitro and organ metastasis in vivo. Int J Mol Med 35(2):425–432. doi: 10.3892/ijmm.2014.2033 PubMedGoogle Scholar
  32. 32.
    Shen PF, Chen XQ, Liao YC, Chen N, Zhou Q, Wei Q, Li X, Wang J, Zeng H (2014) MicroRNA-494-3p targets CXCR4 to suppress the proliferation, invasion, and migration of prostate cancer. Prostate 74(7):756–767. doi: 10.1002/pros.22795 CrossRefPubMedGoogle Scholar
  33. 33.
    Kohlhapp FJ, Mitra AK, Lengyel E, Peter ME (2015) MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment. Oncogene 34(48):5857–5868. doi: 10.1038/onc.2015.89 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Xu B, Wang N, Wang X, Tong N, Shao N, Tao J, Li P, Niu X, Feng N, Zhang L, Hua L, Wang Z, Chen M (2012) MiR-146a suppresses tumor growth and progression by targeting EGFR pathway and in a p-ERK-dependent manner in castration-resistant prostate cancer. Prostate 72(11):1171–1178. doi: 10.1002/pros.22466 CrossRefPubMedGoogle Scholar
  35. 35.
    Chen Q, Zhao X, Zhang H, Yuan H, Zhu M, Sun Q, Lai X, Wang Y, Huang J, Yan J, Yu J (2015) MiR-130b suppresses prostate cancer metastasis through down-regulation of MMP2. Mol Carcinog 54(11):1292–1300. doi: 10.1002/mc.22204 CrossRefPubMedGoogle Scholar
  36. 36.
    Reis ST, Pontes-Junior J, Antunes AA, Dall’Oglio MF, Dip N, Passerotti CC, Rossini GA, Morais DR, Nesrallah AJ, Piantino C, Srougi M, Leite KR (2012) miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer. BMC Urol 12:14. doi: 10.1186/1471-2490-12-14 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Zoni E, van der Horst G, van de Merbel AF, Chen L, Rane JK, Pelger RC, Collins AT, Visakorpi T, Snaar-Jagalska BE, Maitland NJ, van der Pluijm G (2015) miR-25 modulates invasiveness and dissemination of human prostate cancer cells via regulation of αv- and α6-integrin expression. Cancer Res 75(11):2326–2336. doi: 10.1158/0008-5472.CAN-14-2155 CrossRefPubMedGoogle Scholar
  38. 38.
    LeBleu VS, Macdonald B, Kalluri R (2007) Structure and function of basement membranes. Exp Biol Med (Maywood) 232(9):1121–1129CrossRefGoogle Scholar
  39. 39.
    Gandellini P, Profumo V, Casamichele A, Fenderico N, Borrelli S, Petrovich G, Santilli G, Callari M, Colecchia M, Pozzi S, De Cesare M, Folini M, Valdagni R, Mantovani R, Zaffaroni N (2012) miR-205 regulates basement membrane deposition in human prostate: implications for cancer development. Cell Death Differ 19(11):1750–1760. doi: 10.1038/cdd.2012.56 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Cirri P, Chiarugi P (2012) Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression. Cancer Metastasis Rev 31(1–2):195–208. doi: 10.1007/s10555-011-9340-x CrossRefPubMedGoogle Scholar
  41. 41.
    Musumeci M, Coppola V, Addario A, Patrizii M, Maugeri-Saccà M, Memeo L, Colarossi C, Francescangeli F, Biffoni M, Collura D, Giacobbe A, D’Urso L, Falchi M, Venneri MA, Muto G, De Maria R, Bonci D (2011) Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer. Oncogene 30(41):4231–4242. doi: 10.1038/onc.2011.140 CrossRefPubMedGoogle Scholar
  42. 42.
    Gandellini P, Giannoni E, Casamichele A, Taddei ML, Callari M, Piovan C, Valdagni R, Pierotti MA, Zaffaroni N, Chiarugi P (2014) miR-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts. Antioxid Redox Signal 20(7):1045–1059. doi: 10.1089/ars.2013.5292 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Taddei ML, Cavallini L, Comito G, Giannoni E, Folini M, Marini A, Gandellini P, Morandi A, Pintus G, Raspollini MR, Zaffaroni N, Chiarugi P (2014) Senescent stroma promotes prostate cancer progression: the role of miR-210. Mol Oncol 8(8):1729–1746. doi: 10.1016/j.molonc.2014.07.009 CrossRefPubMedGoogle Scholar
  44. 44.
    Josson S, Gururajan M, Sung SY, Hu P, Shao C, Zhau HE, Liu C, Lichterman J, Duan P, Li Q, Rogatko A, Posadas EM, Haga CL, Chung LW (2015) Stromal fibroblast-derived miR-409 promotes epithelial-to-mesenchymal transition and prostate tumorigenesis. Oncogene 34(21):2690–2699. doi: 10.1038/onc.2014.212 CrossRefPubMedGoogle Scholar
  45. 45.
    Doldi V, Callari M, Giannoni E, D’Aiuto F, Maffezzini M, Valdagni R, Chiarugi P, Gandellini P, Zaffaroni N (2015) Integrated gene and miRNA expression analysis of prostate cancer associated fibroblasts supports a prominent role for interleukin-6 in fibroblast activation. Oncotarget 6(31):31441–31460. doi: 10.18632/oncotarget.5056 PubMedPubMedCentralGoogle Scholar
  46. 46.
    Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3(6):401–410CrossRefPubMedGoogle Scholar
  47. 47.
    Liu LZ, Li C, Chen Q, Jing Y, Carpenter R, Jiang Y, Kung HF, Lai L, Jiang BH (2011) MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression. PLoS One 6(4):e19139. doi: 10.1371/journal.pone.0019139 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Taddei ML, Giannoni E, Fiaschi T, Chiarugi P (2012) Anoikis: an emerging hallmark in health and diseases. J Pathol 226(2):380–393. doi: 10.1002/path.3000 CrossRefPubMedGoogle Scholar
  49. 49.
    Formosa A, Lena AM, Markert EK, Cortelli S, Miano R, Mauriello A, Croce N, Vandesompele J, Mestdagh P, Finazzi-Agrò E, Levine AJ, Melino G, Bernardini S, Candi E (2013) DNA methylation silences miR-132 in prostate cancer. Oncogene 32(1):127–134. doi: 10.1038/onc.2012.14 CrossRefPubMedGoogle Scholar
  50. 50.
    Lin ZY, Huang YQ, Zhang YQ, Han ZD, He HC, Ling XH, Fu X, Dai QS, Cai C, Chen JH, Liang YX, Jiang FN, Zhong WD, Wang F, Wu CL (2014) MicroRNA-224 inhibits progression of human prostate cancer by downregulating TRIB1. Int J Cancer 135(3):541–550. doi: 10.1002/ijc.28707 CrossRefPubMedGoogle Scholar
  51. 51.
    Mashima T, Soma-Nagae T, Migita T, Kinoshita R, Iwamoto A, Yuasa T, Yonese J, Ishikawa Y, Seimiya H (2014) TRIB1 supports prostate tumorigenesis and tumor-propagating cell survival by regulation of endoplasmic reticulum chaperone expression. Cancer Res 74(17):4888–4897. doi: 10.1158/0008-5472.CAN-13-3718 CrossRefPubMedGoogle Scholar
  52. 52.
    Takeshita F, Patrawala L, Osaki M, Takahashi RU, Yamamoto Y, Kosaka N, Kawamata M, Kelnar K, Bader AG, Brown D, Ochiya T (2010) Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes. Mol Ther 18(1):181–187. doi: 10.1038/mt.2009.207 CrossRefPubMedGoogle Scholar
  53. 53.
    Peng X, Guo W, Liu T, Wang X, Tu X, Xiong D, Chen S, Lai Y, Du H, Chen G, Liu G, Tang Y, Huang S, Zou X (2011) Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT. PLoS One 6(5):e20341. doi: 10.1371/journal.pone.0020341 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Siu MK, Abou-Kheir W, Yin JJ, Chang YS, Barrett B, Suau F, Casey O, Chen WY, Fang L, Hynes P, Hsieh YY, Liu YN, Huang J, Kelly K (2014) Loss of EGFR signaling regulated miR-203 promotes prostate cancer bone metastasis and tyrosine kinase inhibitors resistance. Oncotarget 5(11):3770–3784CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Chen WY, Liu SY, Chang YS, Yin JJ, Yeh HL, Mouhieddine TH, Hadadeh O, Abou-Kheir W, Liu YN (2015) MicroRNA-34a regulates WNT/TCF7 signaling and inhibits bone metastasis in Ras-activated prostate cancer. Oncotarget 6(1):441–457PubMedGoogle Scholar
  56. 56.
    Liu YN, Yin J, Barrett B, Sheppard-Tillman H, Li D, Casey OM, Fang L, Hynes PG, Ameri AH, Kelly K (2015) Loss of androgen-regulated microRNA 1 activates SRC and promotes prostate cancer bone metastasis. Mol Cell Biol 35(11):1940–1951. doi: 10.1128/MCB.00008-15 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Chang YS, Chen WY, Yin JJ, Sheppard-Tillman H, Huang J, Liu YN (2015) EGF receptor promotes prostate cancer bone metastasis by downregulating miR-1 and activating TWIST1. Cancer Res 75(15):3077–3086. doi: 10.1158/0008-5472.CAN-14-3380 CrossRefPubMedGoogle Scholar
  58. 58.
    Karatas OF, Guzel E, Suer I, Ekici ID, Caskurlu T, Creighton CJ, Ittmann M, Ozen M (2014) miR-1 and miR-133b are differentially expressed in patients with recurrent prostate cancer. PLoS One 9(6):e98675. doi: 10.1371/journal.pone.0098675 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Siu MK, Tsai YC, Chang YS, Yin JJ, Suau F, Chen WY, Liu YN (2015) Transforming growth factor-β promotes prostate bone metastasis through induction of microRNA-96 and activation of the mTOR pathway. Oncogene 34(36):4767–4776. doi: 10.1038/onc.2014.414 CrossRefPubMedGoogle Scholar
  60. 60.
    Gururajan M, Josson S, Chu GC, Lu CL, Lu YT, Haga CL, Zhau HE, Liu C, Lichterman J, Duan P, Posadas EM, Chung LW (2014) miR-154* and miR-379 in the DLK1-DIO3 microRNA mega-cluster regulate epithelial to mesenchymal transition and bone metastasis of prostate cancer. Clin Cancer Res 20(24):6559–6569. doi: 10.1158/1078-0432.CCR-14-1784 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Josson S, Gururajan M, Hu P, Shao C, Chu GY, Zhau HE, Liu C, Lao K, Lu CL, Lu YT, Lichterman J, Nandana S, Li Q, Rogatko A, Berel D, Posadas EM, Fazli L, Sareen D, Chung LW (2014) miR-409-3p/-5p promotes tumorigenesis, epithelial-to-mesenchymal transition, and bone metastasis of human prostate cancer. Clin Cancer Res 20(17):4636–4646. doi: 10.1158/1078-0432.CCR-14-0305 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Bonci D, Coppola V, Patrizii M, Addario A, Cannistraci A, Francescangeli F, Pecci R, Muto G, Collura D, Bedini R, Zeuner A, Valtieri M, Sentinelli S, Benassi MS, Gallucci M, Carlini P, Piccolo S, De Maria R (2015) A microRNA code for prostate cancer metastasis. Oncogene. doi: 10.1038/onc.2015.176 PubMedPubMedCentralGoogle Scholar
  63. 63.
    Hagman Z, Haflidadóttir BS, Ceder JA, Larne O, Bjartell A, Lilja H, Edsjö A, Ceder Y (2013) miR-205 negatively regulates the androgen receptor and is associated with adverse outcome of prostate cancer patients. Br J Cancer 108(8):1668–1676. doi: 10.1038/bjc.2013.131 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Kalogirou C, Spahn M, Krebs M, Joniau S, Lerut E, Burger M, Scholz CJ, Kneitz S, Riedmiller H, Kneitz B (2013) MiR-205 is progressively down-regulated in lymph node metastasis but fails as a prognostic biomarker in high-risk prostate cancer. Int J Mol Sci 14(11):21414–21434. doi: 10.3390/ijms141121414 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Mavridis K, Stravodimos K, Scorilas A (2013) Downregulation and prognostic performance of microRNA 224 expression in prostate cancer. Clin Chem 9(1):261–269. doi: 10.1373/clinchem.2012.191502 CrossRefGoogle Scholar
  66. 66.
    Wan Y, Zeng ZC, Xi M, Wan S, Hua W, Liu YL, Zhou YL, Luo HW, Jiang FN, Zhong WD (2015) Dysregulated microRNA-224/apelin axis associated with aggressive progression and poor prognosis in patients with prostate cancer. Hum Pathol 46(2):295–303. doi: 10.1016/j.humpath.2014.10.027 CrossRefPubMedGoogle Scholar
  67. 67.
    Li T, Li RS, Li YH, Zhong S, Chen YY, Zhang CM, Hu MM, Shen ZJ (2012) miR-21 as an independent biochemical recurrence predictor and potential therapeutic target for prostate cancer. J Urol 187(4):1466–1472. doi: 10.1016/j.juro.2011.11.082 CrossRefPubMedGoogle Scholar
  68. 68.
    Sun X, Liu Z, Yang Z, Xiao L, Wang F, He Y, Su P, Wang J, Jing B (2013) Association of microRNA-126 expression with clinicopathological features and the risk of biochemical recurrence in prostate cancer patients undergoing radical prostatectomy. Diagn Pathol 8:208. doi: 10.1186/1746-1596-8-208 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Forno I, Ferrero S, Russo MV, Gazzano G, Giangiobbe S, Montanari E, Del Nero A, Rocco B, Albo G, Languino LR, Altieri DC, Vaira V, Bosari S (2015) Deregulation of MiR-34b/Sox2 predicts prostate cancer progression. PLoS One 10(6):e0130060. doi: 10.1371/journal.pone.0130060 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E, Reva B, Antipin Y, Mitsiades N, Landers T, Dolgalev I, Major JE, Wilson M, Socci ND, Lash AE, Heguy A, Eastham JA, Scher HI, Reuter VE, Scardino PT, Sander C, Sawyers CL, Gerald WL (2010) Integrative genomic profiling of human prostate cancer. Cancer Cell 18(1):11–22. doi: 10.1016/j.ccr.2010.05.026 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    van Rooij E, Kauppinen S (2014) Development of microRNA therapeutics is coming of age. EMBO Mol Med 6(7):851–864. doi: 10.15252/emmm.201100899 CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Wen D, Danquah M, Chaudhary AK, Mahato RI (2015) Small molecules targeting microRNA for cancer therapy: promises and obstacles. J Control Release 219:237–247. doi: 10.1016/j.jconrel.2015.08.011 CrossRefPubMedGoogle Scholar
  73. 73.
    Liu YP (1809) Berkhout B (2011) miRNA cassettes in viral vectors: problems and solutions. Biochim Biophys Acta 11–12:732–745. doi: 10.1016/j.bbagrm.2011.05.014 Google Scholar
  74. 74.
    Wang Z (2011) The principles of MiRNA-masking antisense oligonucleotides technology. Methods Mol Biol 676:43–49. doi: 10.1007/978-1-60761-863-8_3 CrossRefPubMedGoogle Scholar
  75. 75.
    Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van der Meer AJ, Patick AK, Chen A, Zhou Y, Persson R, King BD, Kauppinen S, Levin AA, Hodges MR (2013) Treatment of HCV infection by targeting microRNA. N Engl J Med 368(18):1685–1694. doi: 10.1056/NEJMoa1209026 CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Valentina Doldi
    • 1
  • Marzia Pennati
    • 1
  • Barbara Forte
    • 1
  • Paolo Gandellini
    • 1
  • Nadia Zaffaroni
    • 1
  1. 1.Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular MedicineFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly

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