Cellular and Molecular Life Sciences

, Volume 70, Issue 20, pp 3773–3789 | Cite as

Deciphering microRNA code in pain and inflammation: lessons from bladder pain syndrome

  • Ali Hashemi Gheinani
  • Fiona C. Burkhard
  • Katia MonastyrskayaEmail author


MicroRNAs (miRNAs), a novel class of molecules regulating gene expression, have been hailed as modulators of many biological processes and disease states. Recent studies demonstrated an important role of miRNAs in the processes of inflammation and cancer, however, there are little data implicating miRNAs in peripheral pain. Bladder pain syndrome/interstitial cystitis (BPS/IC) is a clinical syndrome of pelvic pain and urinary urgency/frequency in the absence of a specific cause. BPS is a chronic inflammatory condition that might share some of the pathogenetic mechanisms with its common co-morbidities inflammatory bowel disease (IBD), asthma and autoimmune diseases. Using miRNA profiling in BPS and the information about validated miRNA targets, we delineated the signaling pathways activated in this and other inflammatory pain disorders. This review projects the miRNA profiling and functional data originating from the research in bladder cancer and immune-mediated diseases on the BPS-specific miRNAs with the aim to gain new insight into the pathogenesis of this enigmatic disorder, and highlighting the common regulatory mechanisms of pain and inflammation.


MicroRNA Bladder Pain Inflammation Gene expression Bladder cancer Inflammatory bowel disease 



We gratefully acknowledge the financial support of the Swiss National Science Foundation (SNF Grant 320030_135783/1 to K. Monastyrskaya).


  1. 1.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. doi: 10.1016/j.cell.2009.01.002 PubMedGoogle Scholar
  2. 2.
    Farazi TA, Spitzer JI, Morozov P, Tuschl T (2011) miRNAs in human cancer. J Pathol 223(2):102–115. doi: 10.1002/path.2806 PubMedGoogle Scholar
  3. 3.
    Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294(5543):853–858. doi: 10.1126/science.1064921 PubMedGoogle Scholar
  4. 4.
    Orom UA, Nielsen FC, Lund AH (2008) MicroRNA-10a binds the 5′UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 30(4):460–471. doi: 10.1016/j.molcel.2008.05.001 PubMedGoogle Scholar
  5. 5.
    Henke JI, Goergen D, Zheng J, Song Y, Schuttler CG, Fehr C, Junemann C, Niepmann M (2008) microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J 27(24):3300–3310. doi: 10.1038/emboj.2008.244 PubMedGoogle Scholar
  6. 6.
    Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I (2008) MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455(7216):1124–1128. doi: 10.1038/nature07299 PubMedGoogle Scholar
  7. 7.
    Huang S, Wu S, Ding J, Lin J, Wei L, Gu J, He X (2010) MicroRNA-181a modulates gene expression of zinc finger family members by directly targeting their coding regions. Nucleic Acids Res 38(20):7211–7218. doi: 10.1093/nar/gkq564 PubMedGoogle Scholar
  8. 8.
    Duursma AM, Kedde M, Schrier M, le Sage C, Agami R (2008) miR-148 targets human DNMT3b protein coding region. RNA 14(5):872–877. doi: 10.1261/rna.972008 PubMedGoogle Scholar
  9. 9.
    Thomson DW, Bracken CP, Goodall GJ (2011) Experimental strategies for microRNA target identification. Nucleic Acids Res 39(16):6845–6853. doi: 10.1093/nar/gkr330 PubMedGoogle Scholar
  10. 10.
    Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854PubMedGoogle Scholar
  11. 11.
    Lu M, Zhang Q, Deng M, Miao J, Guo Y, Gao W, Cui Q (2008) An analysis of human microRNA and disease associations. PLoS ONE 3(10):e3420. doi: 10.1371/journal.pone.0003420 PubMedGoogle Scholar
  12. 12.
    Wilmott JS, Zhang XD, Hersey P, Scolyer RA (2011) The emerging important role of microRNAs in the pathogenesis, diagnosis and treatment of human cancers. Pathology 43(6):657–671. doi: 10.1097/PAT.0b013e32834a7358 PubMedGoogle Scholar
  13. 13.
    Sanchez Freire V, Burkhard FC, Kessler TM, Kuhn A, Draeger A, Monastyrskaya K (2010) MicroRNAs may mediate the down-regulation of neurokinin-1 receptor in chronic bladder pain syndrome. Am J Pathol 176(1):288–303. doi: 10.2353/ajpath.2010.090552 PubMedGoogle Scholar
  14. 14.
    Monastyrskaya K, Sanchez-Freire V, Gheinani AH, Klumpp DJ, Babiychuk EB, Draeger A, Burkhard FC (2012) miR-199a-5p regulates urothelial permeability and may play a role in bladder pain syndrome. Am J Pathol. doi: 10.1016/j.ajpath.2012.10.020 PubMedGoogle Scholar
  15. 15.
    van de Merwe JP (2007) Interstitial cystitis and systemic autoimmune diseases. Nat Clin Pract Urol 4(9):484–491. doi: 10.1038/ncpuro0874 PubMedGoogle Scholar
  16. 16.
    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 PubMedGoogle Scholar
  17. 17.
    Vasudevan S, Tong Y, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318(5858):1931–1934. doi: 10.1126/science.1149460 PubMedGoogle Scholar
  18. 18.
    Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R (2008) MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Nat Acad Sci USA 105(5):1608–1613. doi: 10.1073/pnas.0707594105 PubMedGoogle Scholar
  19. 19.
    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 Nat Acad Sci USA 99(24):15524–15529. doi: 10.1073/pnas.242606799 PubMedGoogle Scholar
  20. 20.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838. doi: 10.1038/nature03702 PubMedGoogle Scholar
  21. 21.
    van Rooij E, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD, Richardson JA, Olson EN (2006) A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Nat Acad Sci USA 103(48):18255–18260. doi: 10.1073/pnas.0608791103 PubMedGoogle Scholar
  22. 22.
    Schaefer A, O’Carroll D, Tan CL, Hillman D, Sugimori M, Llinas R, Greengard P (2007) Cerebellar neurodegeneration in the absence of microRNAs. J Exp Med 204(7):1553–1558. doi: 10.1084/jem.20070823 PubMedGoogle Scholar
  23. 23.
    Lukiw WJ (2007) Micro-RNA speciation in fetal, adult and Alzheimer’s disease hippocampus. NeuroReport 18(3):297–300. doi: 10.1097/WNR.0b013e3280148e8b PubMedGoogle Scholar
  24. 24.
    Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV, Murchison E, Hannon G, Abeliovich A (2007) A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317(5842):1220–1224. doi: 10.1126/science.1140481 PubMedGoogle Scholar
  25. 25.
    Sonkoly E, Wei T, Janson PC, Saaf A, Lundeberg L, Tengvall-Linder M, Norstedt G, Alenius H, Homey B, Scheynius A, Stahle M, Pivarcsi A (2007) MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS ONE 2(7):e610. doi: 10.1371/journal.pone.0000610 PubMedGoogle Scholar
  26. 26.
    Dai Y, Huang YS, Tang M, Lv TY, Hu CX, Tan YH, Xu ZM, Yin YB (2007) Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus 16(12):939–946. doi: 10.1177/0961203307084158 PubMedGoogle Scholar
  27. 27.
    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 PubMedGoogle Scholar
  28. 28.
    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 PubMedGoogle Scholar
  29. 29.
    Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Orum H (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327(5962):198–201. doi: 10.1126/science.1178178 PubMedGoogle Scholar
  30. 30.
    Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136(4):642–655. doi: 10.1016/j.cell.2009.01.035 PubMedGoogle Scholar
  31. 31.
    Chekulaeva M, Filipowicz W (2009) Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Curr Opin Cell Biol 21(3):452–460. doi: 10.1016/ PubMedGoogle Scholar
  32. 32.
    Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10(2):126–139. doi: 10.1038/nrm2632 PubMedGoogle Scholar
  33. 33.
    Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14(10A):1902–1910. doi: 10.1101/gr.2722704 PubMedGoogle Scholar
  34. 34.
    Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature 432(7014):235–240. doi: 10.1038/nature03120 PubMedGoogle Scholar
  35. 35.
    Wang X, Xu X, Ma Z, Huo Y, Xiao Z, Li Y, Wang Y (2011) Dynamic mechanisms for pre-miRNA binding and export by Exportin-5. RNA 17(8):1511–1528. doi: 10.1261/rna.2732611 PubMedGoogle Scholar
  36. 36.
    MacRae IJ, Zhou K, Doudna JA (2007) Structural determinants of RNA recognition and cleavage by Dicer. Nat Struct Mol Biol 14(10):934–940. doi: 10.1038/nsmb1293 PubMedGoogle Scholar
  37. 37.
    Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC (2007) The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell 130(1):89–100. doi: 10.1016/j.cell.2007.06.028 PubMedGoogle Scholar
  38. 38.
    Berezikov E, Chung WJ, Willis J, Cuppen E, Lai EC (2007) Mammalian mirtron genes. Mol Cell 28(2):328–336. doi: 10.1016/j.molcel.2007.09.028 PubMedGoogle Scholar
  39. 39.
    Ruby JG, Jan CH, Bartel DP (2007) Intronic microRNA precursors that bypass Drosha processing. Nature 448 (7149):83-86. 05983S1.htmlGoogle Scholar
  40. 40.
    Havens MA, Reich AA, Duelli DM, Hastings ML (2012) Biogenesis of mammalian microRNAs by a non-canonical processing pathway. Nucleic Acids Res. doi: 10.1093/nar/gks026 Google Scholar
  41. 41.
    Kozomara A, Griffiths-Jones S (2011) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39(Database issue):D152–D157. doi: 10.1093/nar/gkq1027 PubMedGoogle Scholar
  42. 42.
    Griffiths-Jones S (2004) The microRNA Registry. Nucleic Acids Res 32(suppl 1):D109–D111. doi: 10.1093/nar/gkh023 PubMedGoogle Scholar
  43. 43.
    van de Merwe JP, Nordling J, Bouchelouche P, Bouchelouche K, Cervigni M, Daha LK, Elneil S, Fall M, Hohlbrugger G, Irwin P, Mortensen S, van Ophoven A, Osborne JL, Peeker R, Richter B, Riedl C, Sairanen J, Tinzl M, Wyndaele JJ (2008) Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol 53(1):60–67PubMedGoogle Scholar
  44. 44.
    Curhan GC, Speizer FE, Hunter DJ, Curhan SG, Stampfer MJ (1999) Epidemiology of interstitial cystitis: a population based study. J Urol 161(2):549–552PubMedGoogle Scholar
  45. 45.
    Fall M, Oberpenning F, Peeker R (2008) Treatment of bladder pain syndrome/interstitial cystitis 2008: can we make evidence-based decisions? Eur Urol 54(1):65–75PubMedGoogle Scholar
  46. 46.
    Lilly JD, Parsons CL (1990) Bladder surface glycosaminoglycans is a human epithelial permeability barrier. Surg Gynecol Obstet 171(6):493–496PubMedGoogle Scholar
  47. 47.
    Moskowitz MO, Byrne DS, Callahan HJ, Parsons CL, Valderrama E, Moldwin RM (1994) Decreased expression of a glycoprotein component of bladder surface mucin (GP1) in interstitial cystitis. J Urol 151(2):343–345PubMedGoogle Scholar
  48. 48.
    Birder LA, de Groat WC (2007) Mechanisms of disease: involvement of the urothelium in bladder dysfunction. Nat Clin Pract Urol 4(1):46–54. doi: 10.1038/ncpuro0672 PubMedGoogle Scholar
  49. 49.
    Parsons CL (2007) The role of the urinary epithelium in the pathogenesis of interstitial cystitis/prostatitis/urethritis. Urology 69(4 Suppl):9–16PubMedGoogle Scholar
  50. 50.
    Tomaszewski JE, Landis JR, Russack V, Williams TM, Wang LP, Hardy C, Brensinger C, Matthews YL, Abele ST, Kusek JW, Nyberg LM (2001) Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study. Urology 57(6 Suppl 1):67–81PubMedGoogle Scholar
  51. 51.
    Slobodov G, Feloney M, Gran C, Kyker KD, Hurst RE, Culkin DJ (2004) Abnormal expression of molecular markers for bladder impermeability and differentiation in the urothelium of patients with interstitial cystitis. J Urol 171(4):1554–1558PubMedGoogle Scholar
  52. 52.
    Zhang CO, Wang JY, Koch KR, Keay S (2005) Regulation of tight junction proteins and bladder epithelial paracellular permeability by an antiproliferative factor from patients with interstitial cystitis. J Urol 174(6):2382–2387PubMedGoogle Scholar
  53. 53.
    Liu HT, Shie JH, Chen SH, Wang YS, Kuo HC (2012) Differences in mast cell infiltration, E-cadherin, and zonula occludens-1 expression between patients with overactive bladder and interstitial cystitis/bladder pain syndrome. Urology 80 (1):225 e213-228. doi: 10.1016/j.urology.2012.01.047 Google Scholar
  54. 54.
    Sanchez-Freire V, Blanchard MG, Burkhard FC, Kessler TM, Kellenberger S, Monastyrskaya K (2011) Acid-sensing channels in human bladder: expression, function and alterations during bladder pain syndrome. J Urol 186(4):1509–1516. doi: 10.1016/j.juro.2011.05.047 PubMedGoogle Scholar
  55. 55.
    Sadegh MK, Ekman M, Rippe C, Uvelius B, Sward K, Albinsson S (2012) Deletion of Dicer in smooth muscle affects voiding pattern and reduces detrusor contractility and neuroeffector transmission. PLoS ONE 7(4):e35882. doi: 10.1371/journal.pone.0035882 PubMedGoogle Scholar
  56. 56.
    Zhang S, Lv JW, Yang P, Yu Q, Pang J, Wang Z, Guo H, Liu S, Hu J, Li J, Leng J, Huang Y, Ye Z, Wang CY (2012) Loss of dicer exacerbates cyclophosphamide-induced bladder overactivity by enhancing purinergic signaling. Am J Pathol 181(3):937–946. doi: 10.1016/j.ajpath.2012.05.035 PubMedGoogle Scholar
  57. 57.
    Zhu J, Jiang Z, Gao F, Hu X, Zhou L, Chen J, Luo H, Sun J, Wu S, Han Y, Yin G, Chen M, Han Z, Li X, Huang Y, Zhang W, Zhou F, Chen T, Fa P, Wang Y, Sun L, Leng H, Sun F, Liu Y, Ye M, Yang H, Cai Z, Gui Y, Zhang X (2011) A systematic analysis on dna methylation and the expression of both mRNA and microRNA in bladder cancer. PLoS ONE 6(11):e28223. doi: 10.1371/journal.pone.0028223 PubMedGoogle Scholar
  58. 58.
    Theodorescu D (2003) Molecular pathogenesis of urothelial bladder cancer. Histol Histopathol 18(1):259–274PubMedGoogle Scholar
  59. 59.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi: 10.3322/caac.20107 PubMedGoogle Scholar
  60. 60.
    Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P, Sevignani C, Byrne D, Negrini M, Pagano F, Gomella LG, Croce CM, Baffa R (2007) Micro-RNA profiling in kidney and bladder cancers. Urol Oncol 25(5):387–392. doi: 10.1016/j.urolonc.2007.01.019 PubMedGoogle Scholar
  61. 61.
    Dyrskjot L, Ostenfeld MS, Bramsen JB, Silahtaroglu AN, Lamy P, Ramanathan R, Fristrup N, Jensen JL, Andersen CL, Zieger K, Kauppinen S, Ulhoi BP, Kjems J, Borre M, Orntoft TF (2009) Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res 69(11):4851–4860. doi: 10.1158/0008-5472.CAN-08-4043 PubMedGoogle Scholar
  62. 62.
    Neely LA, Rieger-Christ KM, Neto BS, Eroshkin A, Garver J, Patel S, Phung NA, McLaughlin S, Libertino JA, Whitney D, Summerhayes IC (2008) A microRNA expression ratio defining the invasive phenotype in bladder tumors. Urol Oncol 28(1):39–48. doi: 10.1016/j.urolonc.2008.06.006 PubMedGoogle Scholar
  63. 63.
    Catto JW, Miah S, Owen HC, Bryant H, Myers K, Dudziec E, Larre S, Milo M, Rehman I, Rosario DJ, Di Martino E, Knowles MA, Meuth M, Harris AL, Hamdy FC (2009) Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Res 69(21):8472–8481. doi: 10.1158/0008-5472.CAN-09-0744 PubMedGoogle Scholar
  64. 64.
    Ayala de la Pena F, Kanasaki K, Kanasaki M, Tangirala N, Maeda G, Kalluri R (2011) Loss of p53 and acquisition of angiogenic microRNA profile are insufficient to facilitate progression of bladder urothelial carcinoma in situ to invasive carcinoma. J Biol Chem 286(23):20778–20787. doi: 10.1074/jbc.M110.198069 PubMedGoogle Scholar
  65. 65.
    Lin T, Dong W, Huang J, Pan Q, Fan X, Zhang C, Huang L (2009) MicroRNA-143 as a tumor suppressor for bladder cancer. J Urol 181(3):1372–1380. doi: 10.1016/j.juro.2008.10.149 PubMedGoogle Scholar
  66. 66.
    Ichimi T, Enokida H, Okuno Y, Kunimoto R, Chiyomaru T, Kawamoto K, Kawahara K, Toki K, Kawakami K, Nishiyama K, Tsujimoto G, Nakagawa M, Seki N (2009) Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int J Cancer 125(2):345–352. doi: 10.1002/ijc.24390 PubMedGoogle Scholar
  67. 67.
    Song T, Xia W, Shao N, Zhang X, Wang C, Wu Y, Dong J, Cai W, Li H (2010) Differential miRNA expression profiles in bladder urothelial carcinomas. Asian Pac J Cancer Prev 11(4):905–911PubMedGoogle Scholar
  68. 68.
    Han Y, Chen J, Zhao X, Liang C, Wang Y, Sun L, Jiang Z, Zhang Z, Yang R, Li Z, Tang A, Li X, Ye J, Guan Z, Gui Y, Cai Z (2011) MicroRNA expression signatures of bladder cancer revealed by deep sequencing. PLoS ONE 6(3):e18286. doi: 10.1371/journal.pone.0018286 PubMedGoogle Scholar
  69. 69.
    Catto JW, Alcaraz A, Bjartell AS, De Vere White R, Evans CP, Fussel S, Hamdy FC, Kallioniemi O, Mengual L, Schlomm T, Visakorpi T (2011) MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur Urol 59(5):671–681. doi: 10.1016/j.eururo.2011.01.044 PubMedGoogle Scholar
  70. 70.
    Ru Y, Dancik GM, Theodorescu D (2011) Biomarkers for prognosis and treatment selection in advanced bladder cancer patients. Curr Opin Urol 21(5):420–427. doi: 10.1097/MOU.0b013e32834956d6 PubMedGoogle Scholar
  71. 71.
    Wyndaele JJ, Van Dyck J, Toussaint N (2009) Cystoscopy and bladder biopsies in patients with bladder pain syndrome carried out following ESSIC guidelines. Scand J Urol Nephrol 43(6):471–475. doi: 10.3109/00365590903199007 PubMedGoogle Scholar
  72. 72.
    Grover S, Srivastava A, Lee R, Tewari AK, Te AE (2011) Role of inflammation in bladder function and interstitial cystitis. Ther Adv Urol 3(1):19–33. doi: 10.1177/1756287211398255 PubMedGoogle Scholar
  73. 73.
    Keay S (2008) Cell signaling in interstitial cystitis/painful bladder syndrome. Cell Signal 20(12):2174–2179. doi: 10.1016/j.cellsig.2008.06.004 PubMedGoogle Scholar
  74. 74.
    Pang X, Marchand J, Sant GR, Kream RM, Theoharides TC (1995) Increased number of substance P positive nerve fibres in interstitial cystitis. Br J Urol 75(6):744–750PubMedGoogle Scholar
  75. 75.
    Saban R, Saban MR, Nguyen NB, Lu B, Gerard C, Gerard NP, Hammond TG (2000) Neurokinin-1 (NK-1) receptor is required in antigen-induced cystitis. Am J Pathol 156(3):775–780. doi: 10.1016/S0002-9440(10)64944-9 PubMedGoogle Scholar
  76. 76.
    Liu HT, Kuo HC (2012) Increased urine and serum nerve growth factor levels in interstitial cystitis suggest chronic inflammation is involved in the pathogenesis of disease. PLoS ONE 7(9):e44687. doi: 10.1371/journal.pone.0044687 PubMedGoogle Scholar
  77. 77.
    Shie JH, Liu HT, Kuo HC (2012) Increased cell apoptosis of urothelium mediated by inflammation in interstitial cystitis/painful bladder syndrome. Urology 79 (2):484 e487-413. doi: 10.1016/j.urology.2011.09.049
  78. 78.
    O’Connell RM, Rao DS, Baltimore D (2012) microRNA regulation of inflammatory responses. Annu Rev Immunol 30:295–312. doi: 10.1146/annurev-immunol-020711-075013 PubMedGoogle Scholar
  79. 79.
    Dai R, Ahmed SA (2011) MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl Res 157(4):163–179. doi: 10.1016/j.trsl.2011.01.007 PubMedGoogle Scholar
  80. 80.
    Tomankova T, Petrek M, Gallo J, Kriegova E (2011) MicroRNAs: emerging regulators of immune-mediated diseases. Scand J Immunol. doi: 10.1111/j.1365-3083.2011.02650.x PubMedGoogle Scholar
  81. 81.
    O’Neill LA, Sheedy FJ, McCoy CE (2011) MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol 11(3):163–175. doi: 10.1038/nri2957 PubMedGoogle Scholar
  82. 82.
    Iliopoulos D, Hirsch HA, Struhl K (2009) An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139(4):693–706. doi: 10.1016/j.cell.2009.10.014 PubMedGoogle Scholar
  83. 83.
    Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA, Croce CM (2007) Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179(8):5082–5089PubMedGoogle Scholar
  84. 84.
    Tserel L, Runnel T, Kisand K, Pihlap M, Bakhoff L, Kolde R, Peterson H, Vilo J, Peterson P, Rebane A (2011) MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of Toll-like receptor 4. J Biol Chem 286(30):26487–26495. doi: 10.1074/jbc.M110.213561 PubMedGoogle Scholar
  85. 85.
    Allantaz F, Cheng DT, Bergauer T, Ravindran P, Rossier MF, Ebeling M, Badi L, Reis B, Bitter H, D’Asaro M, Chiappe A, Sridhar S, Pacheco GD, Burczynski ME, Hochstrasser D, Vonderscher J, Matthes T (2012) Expression profiling of human immune cell subsets identifies miRNA-mRNA regulatory relationships correlated with cell type specific expression. PLoS ONE 7(1):e29979. doi: 10.1371/journal.pone.0029979 PubMedGoogle Scholar
  86. 86.
    Keller JJ, Chen YK, Lin HC (2012) Comorbidities of bladder pain syndrome/interstitial cystitis: a population-based study. BJU Int. doi: 10.1111/j.1464-410X.2012.11539.x Google Scholar
  87. 87.
    Jiang X (2011) The emerging role of microRNAs in asthma. Mol Cell Biochem 353(1–2):35–40. doi: 10.1007/s11010-011-0771-z PubMedGoogle Scholar
  88. 88.
    Kuhn AR, Schlauch K, Lao R, Halayko AJ, Gerthoffer WT, Singer CA (2010) MicroRNA expression in human airway smooth muscle cells: role of miR-25 in regulation of airway smooth muscle phenotype. Am J Resp Cell Mol Biol 42(4):506–513. doi: 10.1165/rcmb.2009-0123OC Google Scholar
  89. 89.
    Keller JJ, Liu SP, Lin HC (2012) A case-control study on the association between rheumatoid arthritis and bladder pain syndrome/interstitial cystitis. Neurourol Urodyn. doi: 10.1002/nau.22348 Google Scholar
  90. 90.
    van de Merwe JP, Yamada T, Sakamoto Y (2003) Systemic aspects of interstitial cystitis, immunology and linkage with autoimmune disorders. Int J Urol 10(Suppl):S35–S38PubMedGoogle Scholar
  91. 91.
    Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, Reilly J, Ierna M, Fraser AR, Stolarski B, McSharry C, Hueber AJ, Baxter D, Hunter J, Gay S, Liew FY, McInnes IB (2011) MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci USA 108(27):11193–11198. doi: 10.1073/pnas.1019536108 PubMedGoogle Scholar
  92. 92.
    Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, Li Z, Wu Z, Pei G (2009) MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 10(12):1252–1259. doi: 10.1038/ni.1798 PubMedGoogle Scholar
  93. 93.
    Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y, Huang X, Zhou H, de Vries N, Tak PP, Chen S, Shen N (2009) MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum 60(4):1065–1075. doi: 10.1002/art.24436 PubMedGoogle Scholar
  94. 94.
    Siegel SR, Mackenzie J, Chaplin G, Jablonski NG, Griffiths L (2012) Circulating microRNAs involved in multiple sclerosis. Mol Biol Rep 39(5):6219–6225. doi: 10.1007/s11033-011-1441-7 PubMedGoogle Scholar
  95. 95.
    Chelimsky G, Heller E, Buffington CA, Rackley R, Zhang D, Chelimsky T (2012) Co-morbidities of interstitial cystitis. Front Neurosci 6:114. doi: 10.3389/fnins.2012.00114 Google Scholar
  96. 96.
    Pang X, Boucher W, Triadafilopoulos G, Sant GR, Theoharides TC (1996) Mast cell and substance P-positive nerve involvement in a patient with both irritable bowel syndrome and interstitial cystitis. Urology 47(3):436–438. doi: 10.1016/s0090-4295(99)80469-5 PubMedGoogle Scholar
  97. 97.
    Pekow JR, Kwon JH (2012) MicroRNAs in inflammatory bowel disease. Inflamm Bowel Dis 18(1):187–193. doi: 10.1002/ibd.21691 PubMedGoogle Scholar
  98. 98.
    Iborra M, Bernuzzi F, Invernizzi P, Danese S (2012) MicroRNAs in autoimmunity and inflammatory bowel disease: crucial regulators in immune response. Autoimmun Rev 11(5):305–314. doi: 10.1016/j.autrev.2010.07.002 PubMedGoogle Scholar
  99. 99.
    Paraskevi A, Theodoropoulos G, Papaconstantinou I, Mantzaris G, Nikiteas N, Gazouli M (2012) Circulating MicroRNA in inflammatory bowel disease. J Crohns Colitis. doi: 10.1016/j.crohns.2012.02.006 PubMedGoogle Scholar
  100. 100.
    Zwiers A, Kraal L, van de Pouw Kraan TC, Wurdinger T, Bouma G, Kraal G (2012) Cutting edge: a variant of the IL-23R gene associated with inflammatory bowel disease induces loss of microRNA regulation and enhanced protein production. J Immunol 188(4):1573–1577. doi: 10.4049/jimmunol.1101494 PubMedGoogle Scholar
  101. 101.
    Kanaan Z, Rai SN, Eichenberger MR, Barnes C, Dworkin AM, Weller C, Cohen E, Roberts H, Keskey B, Petras RE, Crawford NP, Galandiuk S (2012) Differential microRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer. Hum Mutat 33(3):551–560. doi: 10.1002/humu.22021 PubMedGoogle Scholar
  102. 102.
    Dalal SR, Kwon JH (2010) The role of microRNA in inflammatory bowel disease. Gastroenterol Hepatol (NY) 6(11):714–722Google Scholar
  103. 103.
    Fasseu M, Treton X, Guichard C, Pedruzzi E, Cazals-Hatem D, Richard C, Aparicio T, Daniel F, Soule JC, Moreau R, Bouhnik Y, Laburthe M, Groyer A, Ogier-Denis E (2010) Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease. PLoS One 5 (10). doi: 10.1371/journal.pone.0013160
  104. 104.
    Olaru AV, Selaru FM, Mori Y, Vazquez C, David S, Paun B, Cheng Y, Jin Z, Yang J, Agarwal R, Abraham JM, Dassopoulos T, Harris M, Bayless TM, Kwon J, Harpaz N, Livak F, Meltzer SJ (2011) Dynamic changes in the expression of MicroRNA-31 during inflammatory bowel disease-associated neoplastic transformation. Inflamm Bowel Dis 17(1):221–231. doi: 10.1002/ibd.21359 PubMedGoogle Scholar
  105. 105.
    Clark PM, Dawany N, Dampier W, Byers SW, Pestell RG, Tozeren A (2012) Bioinformatics analysis reveals transcriptome and microRNA signatures and drug repositioning targets for IBD and other autoimmune diseases. Inflamm Bowel Dis 18(12):2315–2333. doi: 10.1002/ibd.22958 PubMedGoogle Scholar
  106. 106.
    Takagi T, Naito Y, Mizushima K, Hirata I, Yagi N, Tomatsuri N, Ando T, Oyamada Y, Isozaki Y, Hongo H, Uchiyama K, Handa O, Kokura S, Ichikawa H, Yoshikawa T (2010) Increased expression of microRNA in the inflamed colonic mucosa of patients with active ulcerative colitis. J Gastroenterol Hepatol 25(Suppl 1):S129–S133. doi: 10.1111/j.1440-1746.2009.06216.x PubMedGoogle Scholar
  107. 107.
    Bingham B, Ajit SK, Blake DR, Samad TA (2009) The molecular basis of pain and its clinical implications in rheumatology. Nat Clin Pract Rheumatol 5(1):28–37. doi: 10.1038/ncprheum0972 PubMedGoogle Scholar
  108. 108.
    Buchheit T, Van de Ven T, Shaw A (2012) Epigenetics and the transition from acute to chronic pain. Pain Med. doi: 10.1111/j.1526-4637.2012.01488.x PubMedGoogle Scholar
  109. 109.
    He Y, Wang ZJ (2012) Let-7 microRNAs and Opioid Tolerance. Front Genet 3:110. doi: 10.3389/fgene.2012.00110 PubMedGoogle Scholar
  110. 110.
    Im YB, Jee MK, Jung JS, Choi JI, Jang JH, Kang SK (2012) miR23b ameliorates neuropathic pain in spinal cord by silencing NADPH oxidase 4. Antioxid Redox Signal 16(10):1046–1060. doi: 10.1089/ars.2011.4224 PubMedGoogle Scholar
  111. 111.
    Kynast KL, Russe OQ, Moser CV, Geisslinger G, Niederberger E (2012) Modulation of central nervous system-specific microRNA-124a alters the inflammatory response in the formalin test in mice. Pain. doi: 10.1016/j.pain.2012.11.010 PubMedGoogle Scholar
  112. 112.
    Sengupta JN, Pochiraju S, Kannampalli P, Bruckert M, Addya S, Yadav P, Miranda A, Shaker R, Banerjee B (2013) MicroRNA-mediated GABA(Aalpha-1) receptor subunit down-regulation in adult spinal cord following neonatal cystitis-induced chronic visceral pain in rats. Pain 154(1):59–70. doi: 10.1016/j.pain.2012.09.002 PubMedGoogle Scholar
  113. 113.
    Orlova IA, Alexander GM, Qureshi RA, Sacan A, Graziano A, Barrett JE, Schwartzman RJ, Ajit SK (2011) MicroRNA modulation in complex regional pain syndrome. J Transl Med 9:195. doi: 10.1186/1479-5876-9-195 PubMedGoogle Scholar
  114. 114.
    Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G (2000) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408(6808):86–89. doi: 10.1038/35040556 PubMedGoogle Scholar
  115. 115.
    Ding Z, Wang X, Khaidakov M, Liu S, Mehta JL (2012) MicroRNA hsa-let-7 g targets lectin-like oxidized low-density lipoprotein receptor-1 expression and inhibits apoptosis in human smooth muscle cells. Exp Biol Med (Maywood) 237(9):1093–1100. doi: 10.1258/ebm.2012.012082 Google Scholar
  116. 116.
    Ji J, Zhao L, Budhu A, Forgues M, Jia HL, Qin LX, Ye QH, Yu J, Shi X, Tang ZY, Wang XW (2010) Let-7 g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. J Hepatol 52(5):690–697. doi: 10.1016/j.jhep.2009.12.025 PubMedGoogle Scholar
  117. 117.
    Wang K, Lin ZQ, Long B, Li JH, Zhou J, Li PF (2012) Cardiac hypertrophy is positively regulated by MicroRNA miR-23a. J Biol Chem 287(1):589–599. doi: 10.1074/jbc.M111.266940 PubMedGoogle Scholar
  118. 118.
    Wada S, Kato Y, Okutsu M, Miyaki S, Suzuki K, Yan Z, Schiaffino S, Asahara H, Ushida T, Akimoto T (2011) Translational suppression of atrophic regulators by microRNA-23a integrates resistance to skeletal muscle atrophy. J Biol Chem 286(44):38456–38465. doi: 10.1074/jbc.M111.271270 PubMedGoogle Scholar
  119. 119.
    Cao M, Seike M, Soeno C, Mizutani H, Kitamura K, Minegishi Y, Noro R, Yoshimura A, Cai L, Gemma A (2012) MiR-23a regulates TGF-beta-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells. Int J Oncol 41(3):869–875. doi: 10.3892/ijo.2012.1535 PubMedGoogle Scholar
  120. 120.
    Zhang H, Hao Y, Yang J, Zhou Y, Li J, Yin S, Sun C, Ma M, Huang Y, Xi JJ (2011) Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis. Nat Commun 2:554. doi: 10.1038/ncomms1555 PubMedGoogle Scholar
  121. 121.
    Rogler CE, Levoci L, Ader T, Massimi A, Tchaikovskaya T, Norel R, Rogler LE (2009) MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone morphogenetic protein signaling and liver stem cell differentiation by targeting Smads. Hepatology 50(2):575–584. doi: 10.1002/hep.22982 PubMedGoogle Scholar
  122. 122.
    Zhu S, Pan W, Song X, Liu Y, Shao X, Tang Y, Liang D, He D, Wang H, Liu W, Shi Y, Harley JB, Shen N, Qian Y (2012) The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB 2, TAB 3 and IKK-alpha. Nat Med 18(7):1077–1086. doi: 10.1038/nm.2815 PubMedGoogle Scholar
  123. 123.
    Huang Z, Chen X, Yu B, He J, Chen D (2012) MicroRNA-27a promotes myoblast proliferation by targeting myostatin. Biochem Biophys Res Commun 423(2):265–269. doi: 10.1016/j.bbrc.2012.05.106 PubMedGoogle Scholar
  124. 124.
    Zhang H, Zuo Z, Lu X, Wang L, Wang H, Zhu Z (2012) MiR-25 regulates apoptosis by targeting Bim in human ovarian cancer. Oncol Rep 27(2):594–598. doi: 10.3892/or.2011.1530 PubMedGoogle Scholar
  125. 125.
    Razumilava N, Bronk SF, Smoot RL, Fingas CD, Werneburg NW, Roberts LR, Mott JL (2012) miR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and promotes apoptosis resistance in cholangiocarcinoma. Hepatology 55(2):465–475. doi: 10.1002/hep.24698 PubMedGoogle Scholar
  126. 126.
    Leeper NJ, Raiesdana A, Kojima Y, Chun HJ, Azuma J, Maegdefessel L, Kundu RK, Quertermous T, Tsao PS, Spin JM (2011) MicroRNA-26a is a novel regulator of vascular smooth muscle cell function. J Cell Physiol 226(4):1035–1043. doi: 10.1002/jcp.22422 PubMedGoogle Scholar
  127. 127.
    Mohamed JS, Lopez MA, Boriek AM (2010) Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3beta. J Biol Chem 285(38):29336–29347. doi: 10.1074/jbc.M110.101147 PubMedGoogle Scholar
  128. 128.
    Dey BK, Gagan J, Yan Z, Dutta A (2012) miR-26a is required for skeletal muscle differentiation and regeneration in mice. Genes Dev 26(19):2180–2191. doi: 10.1101/gad.198085.112 PubMedGoogle Scholar
  129. 129.
    Huang Z, Huang S, Wang Q, Liang L, Ni S, Wang L, Sheng W, He X, Du X (2011) MicroRNA-95 promotes cell proliferation and targets sorting Nexin 1 in human colorectal carcinoma. Cancer Res 71(7):2582–2589. doi: 10.1158/0008-5472.can-10-3032 PubMedGoogle Scholar
  130. 130.
    Dong P, Karaayvaz M, Jia N, Kaneuchi M, Hamada J, Watari H, Sudo S, Ju J, Sakuragi N (2012) Mutant p53 gain-of-function induces epithelial-mesenchymal transition through modulation of the miR-130b-ZEB1 axis. Oncogene. doi: 10.1038/onc.2012.334 Google Scholar
  131. 131.
    Zhang J, Ying ZZ, Tang ZL, Long LQ, Li K (2012) MicroRNA-148a promotes myogenic differentiation by targeting the ROCK1 gene. J Biol Chem 287(25):21093–21101. doi: 10.1074/jbc.M111.330381 PubMedGoogle Scholar
  132. 132.
    Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, Liu L, Jia D, Tian Q, Wu J, Ye Y, Wang Q, Long Z, Zhou Y, Du C, He X, Shi Y (2011) MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res 17(24):7574–7583. doi: 10.1158/1078-0432.ccr-11-1714 PubMedGoogle Scholar
  133. 133.
    Aprelikova O, Palla J, Hibler B, Yu X, Greer YE, Yi M, Stephens R, Maxwell GL, Jazaeri A, Risinger JI, Rubin JS, Niederhuber J (2012) Silencing of miR-148a in cancer-associated fibroblasts results in WNT10B-mediated stimulation of tumor cell motility. Oncogene. doi: 10.1038/onc.2012.351 PubMedGoogle Scholar
  134. 134.
    Zhou L, Qi X, Potashkin JA, Abdul-Karim FW, Gorodeski GI (2008) MicroRNAs miR-186 and miR-150 down-regulate expression of the pro-apoptotic purinergic P2X7 receptor by activation of instability sites at the 3′-untranslated region of the gene that decrease steady-state levels of the transcript. J Biol Chem 283(42):28274–28286. doi: 10.1074/jbc.M802663200 PubMedGoogle Scholar
  135. 135.
    Kato M, Zhang J, Wang M, Lanting L, Yuan H, Rossi JJ, Natarajan R (2007) MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci USA 104(9):3432–3437. doi: 10.1073/pnas.0611192104 PubMedGoogle Scholar
  136. 136.
    Putta S, Lanting L, Sun G, Lawson G, Kato M, Natarajan R (2012) Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. J Am Soc Nephrol 23(3):458–469. doi: 10.1681/asn.2011050485 PubMedGoogle Scholar
  137. 137.
    Song XW, Li Q, Lin L, Wang XC, Li DF, Wang GK, Ren AJ, Wang YR, Qin YW, Yuan WJ, Jing Q (2010) MicroRNAs are dynamically regulated in hypertrophic hearts, and miR-199a is essential for the maintenance of cell size in cardiomyocytes. J Cell Physiol 225(2):437–443. doi: 10.1002/jcp.22217 PubMedGoogle Scholar
  138. 138.
    Kim S, Lee UJ, Kim MN, Lee EJ, Kim JY, Lee MY, Choung S, Kim YJ, Choi YC (2008) MicroRNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2). J Biol Chem 283(26):18158–18166. doi: 10.1074/jbc.M800186200 PubMedGoogle Scholar
  139. 139.
    Sun JY, Huang Y, Li JP, Zhang X, Wang L, Meng YL, Yan B, Bian YQ, Zhao J, Wang WZ, Yang AG, Zhang R (2012) MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting beta-catenin. Biochem Biophys Res Commun 420(4):787–792. doi: 10.1016/j.bbrc.2012.03.075 PubMedGoogle Scholar
  140. 140.
    Zhang Y, He X, Liu Y, Ye Y, Zhang H, He P, Zhang Q, Dong L, Dong J (2012) microRNA-320a inhibits tumor invasion by targeting neuropilin 1 and is associated with liver metastasis in colorectal cancer. Oncol Rep 27(3):685–694. doi: 10.3892/or.2011.1561 PubMedGoogle Scholar
  141. 141.
    Sepramaniam S, Armugam A, Lim KY, Karolina DS, Swaminathan P, Tan JR, Jeyaseelan K (2010) MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia. J Biol Chem 285(38):29223–29230. doi: 10.1074/jbc.M110.144576 PubMedGoogle Scholar
  142. 142.
    Macconi D, Tomasoni S, Romagnani P, Trionfini P, Sangalli F, Mazzinghi B, Rizzo P, Lazzeri E, Abbate M, Remuzzi G, Benigni A (2012) MicroRNA-324-3p Promotes Renal Fibrosis and Is a Target of ACE Inhibition. J Am Soc Nephrol 23(9):1496–1505. doi: 10.1681/asn.2011121144 PubMedGoogle Scholar
  143. 143.
    Guo L, Qiu Z, Wei L, Yu X, Gao X, Jiang S, Tian H, Jiang C, Zhu D (2012) The microRNA-328 regulates hypoxic pulmonary hypertension by targeting at insulin growth factor 1 receptor and L-type calcium channel-alpha1C. Hypertension 59(5):1006–1013. doi: 10.1161/hypertensionaha.111.185413 PubMedGoogle Scholar
  144. 144.
    Knezevic I, Patel A, Sundaresan NR, Gupta MP, Solaro RJ, Nagalingam RS, Gupta M (2012) A novel cardiomyocyte-enriched microRNA, miR-378, targets insulin-like growth factor 1 receptor: implications in postnatal cardiac remodeling and cell survival. J Biol Chem 287(16):12913–12926. doi: 10.1074/jbc.M111.331751 PubMedGoogle Scholar
  145. 145.
    Yang X, Feng M, Jiang X, Wu Z, Li Z, Aau M, Yu Q (2009) miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 activity through a feedback loop by targeting CDK6 and CDC25A. Genes Dev 23(20):2388–2393. doi: 10.1101/gad.1819009 PubMedGoogle Scholar
  146. 146.
    Ueno K, Hirata H, Majid S, Yamamura S, Shahryari V, Tabatabai ZL, Hinoda Y, Dahiya R (2012) Tumor suppressor microRNA-493 decreases cell motility and migration ability in human bladder cancer cells by downregulating RhoC and FZD4. Mol Cancer Ther 11(1):244–253. doi: 10.1158/1535-7163.mct-11-0592 PubMedGoogle Scholar
  147. 147.
    Okamoto K, Ishiguro T, Midorikawa Y, Ohata H, Izumiya M, Tsuchiya N, Sato A, Sakai H, Nakagama H (2012) miR-493 induction during carcinogenesis blocks metastatic settlement of colon cancer cells in liver. EMBO J 31(7):1752–1763. doi: 10.1038/emboj.2012.25 PubMedGoogle Scholar
  148. 148.
    Rieder F, Kessler SP, West GA, Bhilocha S, de la Motte C, Sadler TM, Gopalan B, Stylianou E, Fiocchi C (2011) Inflammation-induced endothelial-to-mesenchymal transition: a novel mechanism of intestinal fibrosis. Am J Pathol 179(5):2660–2673. doi: 10.1016/j.ajpath.2011.07.042 PubMedGoogle Scholar
  149. 149.
    Richter B, Roslind A, Hesse U, Nordling J, Johansen JS, Horn T, Hansen AB (2010) YKL-40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis. Histopathology 57(3):371–383. doi: 10.1111/j.1365-2559.2010.03640.x PubMedGoogle Scholar
  150. 150.
    Wu F, Zikusoka M, Trindade A, Dassopoulos T, Harris ML, Bayless TM, Brant SR, Chakravarti S, Kwon JH (2008) MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2 alpha. Gastroenterology 135 (5):1624-1635 e1624. doi: 10.1053/j.gastro.2008.07.068
  151. 151.
    Wu F, Zhang S, Dassopoulos T, Harris ML, Bayless TM, Meltzer SJ, Brant SR, Kwon JH (2010) Identification of microRNAs associated with ileal and colonic Crohn’s disease. Inflamm Bowel Dis 16(10):1729–1738. doi: 10.1002/ibd.21267 PubMedGoogle Scholar
  152. 152.
    Sanchez-Simon FM, Zhang XX, Loh HH, Law PY, Rodriguez RE (2010) Morphine regulates dopaminergic neuron differentiation via miR-133b. Mol Pharmacol 78(5):935–942. doi: 10.1124/mol.110.066837 PubMedGoogle Scholar
  153. 153.
    Wu F, Guo NJ, Tian H, Marohn M, Gearhart S, Bayless TM, Brant SR, Kwon JH (2011) Peripheral blood microRNAs distinguish active ulcerative colitis and Crohn’s disease. Inflamm Bowel Dis 17(1):241–250. doi: 10.1002/ibd.21450 PubMedGoogle Scholar
  154. 154.
    Zhou Q, Gallagher R, Ufret-Vincenty R, Li X, Olson EN, Wang S (2011) Regulation of angiogenesis and choroidal neovascularization by members of microRNA-23~27~24 clusters. Proc Natl Acad Sci USA 108(20):8287–8292. doi: 10.1073/pnas.1105254108 PubMedGoogle Scholar
  155. 155.
    Lu J, He ML, Wang L, Chen Y, Liu X, Dong Q, Chen YC, Peng Y, Yao KT, Kung HF, Li XP (2011) MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2. Cancer Res 71(1):225–233. doi: 10.1158/0008-5472.can-10-1850 PubMedGoogle Scholar
  156. 156.
    Ma Y, Yu S, Zhao W, Lu Z, Chen J (2010) miR-27a regulates the growth, colony formation and migration of pancreatic cancer cells by targeting Sprouty2. Cancer Lett 298(2):150–158. doi: 10.1016/j.canlet.2010.06.012 PubMedGoogle Scholar
  157. 157.
    Lai KW, Koh KX, Loh M, Tada K, Subramaniam MM, Lim XY, Vaithilingam A, Salto-Tellez M, Iacopetta B, Ito Y, Soong R (2010) MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer. Eur J Cancer 46(8):1456–1463. doi: 10.1016/j.ejca.2010.01.036 PubMedGoogle Scholar
  158. 158.
    Patron JP, Fendler A, Bild M, Jung U, Muller H, Arntzen MO, Piso C, Stephan C, Thiede B, Mollenkopf HJ, Jung K, Kaufmann SH, Schreiber J (2012) MiR-133b targets antiapoptotic genes and enhances death receptor-induced apoptosis. PLoS ONE 7(4):e35345. doi: 10.1371/journal.pone.0035345 PubMedGoogle Scholar
  159. 159.
    Xie L, Ushmorov A, Leithauser F, Guan H, Steidl C, Farbinger J, Pelzer C, Vogel MJ, Maier HJ, Gascoyne RD, Moller P, Wirth T (2012) FOXO1 is a tumor suppressor in classical Hodgkin lymphoma. Blood 119(15):3503–3511. doi: 10.1182/blood-2011-09-381905 PubMedGoogle Scholar
  160. 160.
    Kong WQ, Bai R, Liu T, Cai CL, Liu M, Li X, Tang H (2012) MicroRNA-182 targets cAMP-responsive element-binding protein 1 and suppresses cell growth in human gastric adenocarcinoma. FEBS J 279(7):1252–1260. doi: 10.1111/j.1742-4658.2012.08519.x PubMedGoogle Scholar
  161. 161.
    Rane S, He M, Sayed D, Vashistha H, Malhotra A, Sadoshima J, Vatner DE, Vatner SF, Abdellatif M (2009) Downregulation of miR-199a derepresses hypoxia-inducible factor-1 alpha and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ Res 104(7):879–886. doi: 10.1161/circresaha.108.193102 PubMedGoogle Scholar
  162. 162.
    Shen Q, Cicinnati VR, Zhang X, Iacob S, Weber F, Sotiropoulos GC, Radtke A, Lu M, Paul A, Gerken G, Beckebaum S (2010) Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion. Mol Cancer 9:227. doi: 10.1186/1476-4598-9-227 PubMedGoogle Scholar
  163. 163.
    Haenisch S, Laechelt S, Bruckmueller H, Werk A, Noack A, Bruhn O, Remmler C, Cascorbi I (2011) Down-regulation of ATP-binding cassette C2 protein expression in HepG2 cells after rifampicin treatment is mediated by microRNA-379. Mol Pharmacol 80(2):314–320. doi: 10.1124/mol.110.070714 PubMedGoogle Scholar
  164. 164.
    Faltejskova P, Svoboda M, Srutova K, Mlcochova J, Besse A, Nekvindova J, Radova L, Fabian P, Slaba K, Kiss I, Vyzula R, Slaby O (2012) Identification and functional screening of microRNAs highly deregulated in colorectal cancer. J Cell Mol Med 16(11):2655–2666. doi: 10.1111/j.1582-4934.2012.01579.x PubMedGoogle Scholar
  165. 165.
    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(51):20350–20355. doi: 10.1073/pnas.0706901104 PubMedGoogle Scholar

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Ali Hashemi Gheinani
    • 1
  • Fiona C. Burkhard
    • 2
  • Katia Monastyrskaya
    • 1
    Email author
  1. 1.Department of Clinical Research, Urology Research LaboratoryUniversity of BernBernSwitzerland
  2. 2.Department of UrologyUniversity HospitalBernSwitzerland

Personalised recommendations