Advertisement

Cellular and Molecular Life Sciences

, Volume 70, Issue 5, pp 795–814 | Cite as

The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis

  • Leonidas Benetatos
  • Eleftheria Hatzimichael
  • Eric Londin
  • George Vartholomatos
  • Phillipe Loher
  • Isidore Rigoutsos
  • Evangelos Briasoulis
Review

Abstract

The mammalian genome is transcribed in a developmentally regulated manner, generating RNA strands ranging from long to short non-coding RNA (ncRNAs). NcRNAs generated by intergenic sequences and protein-coding loci, represent up to 98 % of the human transcriptome. Non-coding transcripts comprise short ncRNAs such as microRNAs, piwi-interacting RNAs, small nucleolar RNAs and long intergenic RNAs, most of which exercise a strictly controlled negative regulation of expression of protein-coding genes. In humans, the DLK1-DIO3 genomic region, located on human chromosome 14 (14q32) contains the paternally expressed imprinted genes DLK1, RTL1, and DIO3 and the maternally expressed imprinted genes MEG3 (Gtl2), MEG8 (RIAN), and antisense RTL1 (asRTL1). This region hosts, in addition to two long intergenic RNAs, the MEG3 and MEG8, one of the largest microRNA clusters in the genome, with 53 miRNAs in the forward strand and one (mir-1247) in the reverse strand. Many of these miRNAs are differentially expressed in several pathologic processes and various cancers. A better understanding of the pathophysiologic importance of the DLK1-DIO3 domain-containing microRNA cluster may contribute to innovative therapeutic strategies in a range of diseases. Here we present an in-depth review of this vital genomic region, and examine the role the microRNAs of this region may play in controlling tissue homeostasis and in the pathogenesis of some human diseases, mostly cancer, when aberrantly expressed. The potential clinical implications of this data are also discussed.

Keywords

DLK1-DIO3 Long non-coding RNA microRNAs Cancer Signaling pathways Transcriptional regulatory pathways 

Notes

Acknowledgments

E.H. is a scholar of the Hellenic Society of Haematology Foundation. P.L. and I.R. are partially supported by a William M. Keck Foundation grant.

Conflict of interest

The authors declare no potential conflicts of interest.

References

  1. 1.
    Shabalina SA, Spiridonov NA (2004) The mammalian transcriptome and the function of non-coding DNA sequences. Genome Biol 5(4):105. doi: 10.1186/gb-2004-5-4-105 PubMedCrossRefGoogle Scholar
  2. 2.
    Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS (2010) Non-coding RNAs: regulators of disease. J Pathol 220(2):126–139. doi: 10.1002/path.2638 PubMedCrossRefGoogle Scholar
  3. 3.
    Mattick JS (2009) The genetic signatures of noncoding RNAs. PLoS Genet 5(4):e1000459. doi: 10.1371/journal.pgen.1000459 PubMedCrossRefGoogle Scholar
  4. 4.
    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 PubMedCrossRefGoogle Scholar
  5. 5.
    Rother S, Meister G (2011) Small RNAs derived from longer non-coding RNAs. Biochimie 93(11):1905–1915. doi: 10.1016/j.biochi.2011.07.032 PubMedCrossRefGoogle Scholar
  6. 6.
    Tollervey D, Kiss T (1997) Function and synthesis of small nucleolar RNAs. Curr Opin Cell Biol 9(3):337–342PubMedCrossRefGoogle Scholar
  7. 7.
    Kiss T (2002) Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular functions. Cell 109(2):145–148PubMedCrossRefGoogle Scholar
  8. 8.
    Zhou H, Hu H, Lai M (2010) Non-coding RNAs and their epigenetic regulatory mechanisms. Biol Cell Auspices Eur Cell Biol Organ 102(12):645–655. doi: 10.1042/BC20100029 Google Scholar
  9. 9.
    Koerner MV, Pauler FM, Huang R, Barlow DP (2009) The function of non-coding RNAs in genomic imprinting. Development 136(11):1771–1783. doi: 10.1242/dev.030403 PubMedCrossRefGoogle Scholar
  10. 10.
    Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458(7235):223–227. doi: 10.1038/nature07672 PubMedCrossRefGoogle Scholar
  11. 11.
    Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang Q, Guigo R, Shiekhattar R (2010) Long noncoding RNAs with enhancer-like function in human cells. Cell 143(1):46–58. doi: 10.1016/j.cell.2010.09.001 PubMedCrossRefGoogle Scholar
  12. 12.
    Tsai MC, Spitale RC, Chang HY (2011) Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res 71(1):3–7. doi: 10.1158/0008-5472.CAN-10-2483 PubMedCrossRefGoogle Scholar
  13. 13.
    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076. doi: 10.1038/nature08975 PubMedCrossRefGoogle Scholar
  14. 14.
    Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, Young G, Lucas AB, Ach R, Bruhn L, Yang X, Amit I, Meissner A, Regev A, Rinn JL, Root DE, Lander ES (2011) lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477(7364):295–300. doi: 10.1038/nature10398 PubMedCrossRefGoogle Scholar
  15. 15.
    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 PubMedCrossRefGoogle Scholar
  16. 16.
    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 PubMedCrossRefGoogle Scholar
  17. 17.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297PubMedCrossRefGoogle Scholar
  18. 18.
    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 PubMedCrossRefGoogle Scholar
  19. 19.
    Cheloufi S, Dos Santos CO, Chong MM, Hannon GJ (2010) A dicer-independent miRNA biogenesis pathway that requires ago catalysis. Nature 465(7298):584–589. doi: 10.1038/nature09092 PubMedCrossRefGoogle Scholar
  20. 20.
    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 PubMedCrossRefGoogle Scholar
  21. 21.
    Ichimura A, Ruike Y, Terasawa K, Tsujimoto G (2011) miRNAs and regulation of cell signaling. FEBS J 278(10):1610–1618. doi: 10.1111/j.1742-4658.2011.08087.x PubMedCrossRefGoogle Scholar
  22. 22.
    He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM (2005) A microRNA polycistron as a potential human oncogene. Nature 435(7043):828–833. doi: 10.1038/nature03552 PubMedCrossRefGoogle Scholar
  23. 23.
    Medina PP, Nolde M, Slack FJ (2010) OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 467(7311):86–90. doi: 10.1038/nature09284 PubMedCrossRefGoogle Scholar
  24. 24.
    Melo SA, Esteller M (2011) Dysregulation of microRNAs in cancer: playing with fire. FEBS Lett 585(13):2087–2099. doi: 10.1016/j.febslet.2010.08.009 PubMedCrossRefGoogle Scholar
  25. 25.
    Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101(9):2999–3004. doi: 10.1073/pnas.0307323101 PubMedCrossRefGoogle Scholar
  26. 26.
    Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6(11):857–866. doi: 10.1038/nrc1997 PubMedCrossRefGoogle Scholar
  27. 27.
    Benetatos L, Vartholomatos G (2012) Deregulated microRNAs in multiple myeloma. Cancer 118(4):878–887. doi: 10.1002/cncr.26297 PubMedCrossRefGoogle Scholar
  28. 28.
    Calvo KR, Landgren O, Roccaro AM, Ghobrial IM (2011) Role of microRNAs from monoclonal gammopathy of undetermined significance to multiple myeloma. Semin Hematol 48(1):39–45. doi: 10.1053/j.seminhematol.2010.11.007 PubMedCrossRefGoogle Scholar
  29. 29.
    Marcucci G, Mrozek K, Radmacher MD, Garzon R, Bloomfield CD (2011) The prognostic and functional role of microRNAs in acute myeloid leukemia. Blood 117(4):1121–1129. doi: 10.1182/blood-2010-09-191312 PubMedCrossRefGoogle Scholar
  30. 30.
    Rhyasen GW, Starczynowski DT (2012) Deregulation of microRNAs in myelodysplastic syndrome. Leuk Off J Leuk Soc Am Leuk Res Fund UK 26(1):13–22. doi: 10.1038/leu.2011.221 CrossRefGoogle Scholar
  31. 31.
    Chira P, Vareli K, Sainis I, Papandreou C, Briasoulis E (2010) Alterations of MicroRNAs in solid cancers and their prognostic value. Cancers 2(2):1328–1353. doi: 10.3390/cancers2021328 CrossRefGoogle Scholar
  32. 32.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838. doi: 10.1038/nature03702 PubMedCrossRefGoogle Scholar
  33. 33.
    Schmidt JV, Matteson PG, Jones BK, Guan XJ, Tilghman SM (2000) The Dlk1 and Gtl2 genes are linked and reciprocally imprinted. Gene Dev 14(16):1997–2002PubMedGoogle Scholar
  34. 34.
    Irving MD, Buiting K, Kanber D, Donaghue C, Schulz R, Offiah A, Mohammed SN, Oakey RJ (2010) Segmental paternal uniparental disomy (patUPD) of 14q32 with abnormal methylation elicits the characteristic features of complete patUPD14. Am J Med Genet Part A 152A(8):1942–1950. doi: 10.1002/ajmg.a.33449 PubMedCrossRefGoogle Scholar
  35. 35.
    Edwards CA, Mungall AJ, Matthews L, Ryder E, Gray DJ, Pask AJ, Shaw G, Graves JA, Rogers J, Dunham I, Renfree MB, Ferguson-Smith AC (2008) The evolution of the DLK1-DIO3 imprinted domain in mammals. PLoS Biol 6(6):e135. doi: 10.1371/journal.pbio.0060135 PubMedCrossRefGoogle Scholar
  36. 36.
    Kagami M, O’Sullivan MJ, Green AJ, Watabe Y, Arisaka O, Masawa N, Matsuoka K, Fukami M, Matsubara K, Kato F, Ferguson-Smith AC, Ogata T (2010) The IG-DMR and the MEG3-DMR at human chromosome 14q32.2: hierarchical interaction and distinct functional properties as imprinting control centers. PLoS Genet 6(6):e1000992. doi: 10.1371/journal.pgen.1000992 PubMedCrossRefGoogle Scholar
  37. 37.
    da Rocha ST, Edwards CA, Ito M, Ogata T, Ferguson-Smith AC (2008) Genomic imprinting at the mammalian Dlk1-Dio3 domain. Trends Genet TIG 24(6):306–316. doi: 10.1016/j.tig.2008.03.011 CrossRefGoogle Scholar
  38. 38.
    Zhou Y, Zhang X, Klibanski A (2012) MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol 48(3):R45–R53. doi: 10.1530/JME-12-0008 PubMedCrossRefGoogle Scholar
  39. 39.
    Benetatos L, Vartholomatos G, Hatzimichael E (2011) MEG3 imprinted gene contribution in tumorigenesis. Int J Cancer J Int du cancer 129(4):773–779. doi: 10.1002/ijc.26052 CrossRefGoogle Scholar
  40. 40.
    Takahashi N, Okamoto A, Kobayashi R, Shirai M, Obata Y, Ogawa H, Sotomaru Y, Kono T (2009) Deletion of Gtl2, imprinted non-coding RNA, with its differentially methylated region induces lethal parent-origin-dependent defects in mice. Hum Mol Genet 18(10):1879–1888. doi: 10.1093/hmg/ddp108 PubMedCrossRefGoogle Scholar
  41. 41.
    Zhou Y, Cheunsuchon P, Nakayama Y, Lawlor MW, Zhong Y, Rice KA, Zhang L, Zhang X, Gordon FE, Lidov HG, Bronson RT, Klibanski A (2010) Activation of paternally expressed genes and perinatal death caused by deletion of the Gtl2 gene. Development 137(16):2643–2652. doi: 10.1242/dev.045724 PubMedCrossRefGoogle Scholar
  42. 42.
    Gordon FE, Nutt CL, Cheunsuchon P, Nakayama Y, Provencher KA, Rice KA, Zhou Y, Zhang X, Klibanski A (2010) Increased expression of angiogenic genes in the brains of mouse meg3-null embryos. Endocrinology 151(6):2443–2452. doi: 10.1210/en.2009-1151 PubMedCrossRefGoogle Scholar
  43. 43.
    Liu L, Luo GZ, Yang W, Zhao X, Zheng Q, Lv Z, Li W, Wu HJ, Wang L, Wang XJ, Zhou Q (2010) Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells. J Biol Chem 285(25):19483–19490. doi: 10.1074/jbc.M110.131995 PubMedCrossRefGoogle Scholar
  44. 44.
    Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S, Negrini M, Miotto E, Croce CM, Patel T (2011) microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene 30(47):4750–4756. doi: 10.1038/onc.2011.193 PubMedCrossRefGoogle Scholar
  45. 45.
    Glazov EA, McWilliam S, Barris WC, Dalrymple BP (2008) Origin, evolution, and biological role of miRNA cluster in DLK-DIO3 genomic region in placental mammals. Mol Biol Evol 25(5):939–948. doi: 10.1093/molbev/msn045 PubMedCrossRefGoogle Scholar
  46. 46.
    Seitz H, Royo H, Bortolin ML, Lin SP, Ferguson-Smith AC, Cavaille J (2004) A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Res 14(9):1741–1748. doi: 10.1101/gr.2743304 PubMedCrossRefGoogle Scholar
  47. 47.
    Hagan JP, O’Neill BL, Stewart CL, Kozlov SV, Croce CM (2009) At least ten genes define the imprinted Dlk1-Dio3 cluster on mouse chromosome 12qF1. PLoS One 4(2):e4352. doi: 10.1371/journal.pone.0004352 PubMedCrossRefGoogle Scholar
  48. 48.
    Song G, Wang L (2008) MiR-433 and miR-127 arise from independent overlapping primary transcripts encoded by the miR-433-127 locus. PLoS One 3(10):e3574. doi: 10.1371/journal.pone.0003574 PubMedCrossRefGoogle Scholar
  49. 49.
    Song G, Wang L (2008) Transcriptional mechanism for the paired miR-433 and miR-127 genes by nuclear receptors SHP and ERRgamma. Nucleic Acids Res 36(18):5727–5735. doi: 10.1093/nar/gkn567 PubMedCrossRefGoogle Scholar
  50. 50.
    Song G, Wang L (2009) A conserved gene structure and expression regulation of miR-433 and miR-127 in mammals. PLoS One 4(11):e7829. doi: 10.1371/journal.pone.0007829 PubMedCrossRefGoogle Scholar
  51. 51.
    Seitz H, Youngson N, Lin SP, Dalbert S, Paulsen M, Bachellerie JP, Ferguson-Smith AC, Cavaille J (2003) Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-like gene. Nat Genet 34(3):261–262. doi: 10.1038/ng1171 PubMedCrossRefGoogle Scholar
  52. 52.
    Sekita Y, Wagatsuma H, Nakamura K, Ono R, Kagami M, Wakisaka N, Hino T, Suzuki-Migishima R, Kohda T, Ogura A, Ogata T, Yokoyama M, Kaneko-Ishino T, Ishino F (2008) Role of retrotransposon-derived imprinted gene, Rtl1, in the feto-maternal interface of mouse placenta. Nat Genet 40(2):243–248. doi: 10.1038/ng.2007.51 PubMedCrossRefGoogle Scholar
  53. 53.
    Cui XS, Zhang DX, Ko YG, Kim NH (2009) Aberrant epigenetic reprogramming of imprinted microRNA-127 and Rtl1 in cloned mouse embryos. Biochem Biophys Res Commun 379(2):390–394. doi: 10.1016/j.bbrc.2008.12.148 PubMedCrossRefGoogle Scholar
  54. 54.
    Gao J, Wang WY, Mao YW, Graff J, Guan JS, Pan L, Mak G, Kim D, Su SC, Tsai LH (2010) A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature 466(7310):1105–1109. doi: 10.1038/nature09271 PubMedCrossRefGoogle Scholar
  55. 55.
    Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439(7074):283–289. doi: 10.1038/nature04367 PubMedCrossRefGoogle Scholar
  56. 56.
    Tay YM, Tam WL, Ang YS, Gaughwin PM, Yang H, Wang W, Liu R, George J, Ng HH, Perera RJ, Lufkin T, Rigoutsos I, Thomson AM, Lim B (2008) MicroRNA-134 modulates the differentiation of mouse embryonic stem cells, where it causes post-transcriptional attenuation of Nanog and LRH1. Stem Cells 26(1):17–29. doi: 10.1634/stemcells.2007-0295 PubMedCrossRefGoogle Scholar
  57. 57.
    Mellios N, Huang HS, Grigorenko A, Rogaev E, Akbarian S (2008) A set of differentially expressed miRNAs, including miR-30a-5p, act as post-transcriptional inhibitors of BDNF in prefrontal cortex. Hum Mol Genet 17(19):3030–3042. doi: 10.1093/hmg/ddn201 PubMedCrossRefGoogle Scholar
  58. 58.
    Zhang J, Zhang J, Liu LH, Zhou Y, Li YP, Shao ZH, Wu YJ, Li MJ, Fan YY, Shi HJ (2011) Effects of miR-541 on neurite outgrowth during neuronal differentiation. Cell Biochem Funct 29(4):279–286. doi: 10.1002/cbf.1747 PubMedCrossRefGoogle Scholar
  59. 59.
    Fiore R, Khudayberdiev S, Christensen M, Siegel G, Flavell SW, Kim TK, Greenberg ME, Schratt G (2009) Mef2-mediated transcription of the miR379-410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels. EMBO J 28(6):697–710. doi: 10.1038/emboj.2009.10 PubMedCrossRefGoogle Scholar
  60. 60.
    Simion A, Laudadio I, Prevot PP, Raynaud P, Lemaigre FP, Jacquemin P (2010) MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2. Biochem Biophys Res Commun 391(1):293–298. doi: 10.1016/j.bbrc.2009.11.052 PubMedCrossRefGoogle Scholar
  61. 61.
    Tominaga K, Srikantan S, Lee EK, Subaran SS, Martindale JL, Abdelmohsen K, Gorospe M (2011) Competitive regulation of nucleolin expression by HuR and miR-494. Mol Cell Biol 31(20):4219–4231. doi: 10.1128/MCB.05955-11 PubMedCrossRefGoogle Scholar
  62. 62.
    Williams AE, Moschos SA, Perry MM, Barnes PJ, Lindsay MA (2007) Maternally imprinted microRNAs are differentially expressed during mouse and human lung development. Dev Dyn Off Publ Am Assoc Anat 236(2):572–580. doi: 10.1002/dvdy.21047 Google Scholar
  63. 63.
    Choong ML, Yang HH, McNiece I (2007) MicroRNA expression profiling during human cord blood-derived CD34 cell erythropoiesis. Exp Hematol 35(4):551–564. doi: 10.1016/j.exphem.2006.12.002 PubMedCrossRefGoogle Scholar
  64. 64.
    Wang F, Yu J, Yang GH, Wang XS, Zhang JW (2011) Regulation of erythroid differentiation by miR-376a and its targets. Cell Res 21(8):1196–1209. doi: 10.1038/cr.2011.79 PubMedCrossRefGoogle Scholar
  65. 65.
    Beckman JD, Chen C, Nguyen J, Thayanithy V, Subramanian S, Steer CJ, Vercellotti GM (2011) Regulation of heme oxygenase-1 protein expression by miR-377 in combination with miR-217. J Biol Chem 286(5):3194–3202. doi: 10.1074/jbc.M110.148726 PubMedCrossRefGoogle Scholar
  66. 66.
    Teferedegne B, Murata H, Quinones M, Peden K, Lewis AM (2010) Patterns of microRNA expression in non-human primate cells correlate with neoplastic development in vitro. PLoS One 5(12):e14416. doi: 10.1371/journal.pone.0014416 PubMedCrossRefGoogle Scholar
  67. 67.
    Chien WW, Domenech C, Catallo R, Kaddar T, Magaud JP, Salles G, Ffrench M (2011) Cyclin-dependent kinase 1 expression is inhibited by p16(INK4a) at the post-transcriptional level through the microRNA pathway. Oncogene 30(16):1880–1891. doi: 10.1038/onc.2010.570 PubMedCrossRefGoogle Scholar
  68. 68.
    Lee YN, Brandal S, Noel P, Wentzel E, Mendell JT, McDevitt MA, Kapur R, Carter M, Metcalfe DD, Takemoto CM (2011) KIT signaling regulates MITF expression through miRNAs in normal and malignant mast cell proliferation. Blood 117(13):3629–3640. doi: 10.1182/blood-2010-07-293548 PubMedCrossRefGoogle Scholar
  69. 69.
    Chen CF, He X, Arslan AD, Mo YY, Reinhold WC, Pommier Y, Beck WT (2011) Novel regulation of nuclear factor-YB by miR-485-3p affects the expression of DNA topoisomerase IIalpha and drug responsiveness. Mol Pharmacol 79(4):735–741. doi: 10.1124/mol.110.069633 PubMedCrossRefGoogle Scholar
  70. 70.
    Meng F, Wehbe-Janek H, Henson R, Smith H, Patel T (2008) Epigenetic regulation of microRNA-370 by interleukin-6 in malignant human cholangiocytes. Oncogene 27(3):378–386. doi: 10.1038/sj.onc.1210648 PubMedCrossRefGoogle Scholar
  71. 71.
    Olaru AV, Ghiaur G, Yamanaka S, Luvsanjav D, An F, Popescu I, Alexandrescu S, Allen S, Pawlik TM, Torbenson M, Georgiades C, Roberts LR, Gores GJ, Ferguson-Smith A, Almeida MI, Calin GA, Mezey E, Selaru FM (2011) MicroRNA down-regulated in human cholangiocarcinoma control cell cycle through multiple targets involved in the G1/S checkpoint. Hepatology 54(6):2089–2098. doi: 10.1002/hep.24591 PubMedCrossRefGoogle Scholar
  72. 72.
    Li Z, Lu J, Sun M, Mi S, Zhang H, Luo RT, Chen P, Wang Y, Yan M, Qian Z, Neilly MB, Jin J, Zhang Y, Bohlander SK, Zhang DE, Larson RA, Le Beau MM, Thirman MJ, Golub TR, Rowley JD, Chen J (2008) Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci USA 105(40):15535–15540. doi: 10.1073/pnas.0808266105 PubMedCrossRefGoogle Scholar
  73. 73.
    Dixon-McIver A, East P, Mein CA, Cazier JB, Molloy G, Chaplin T, Andrew Lister T, Young BD, Debernardi S (2008) Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia. PLoS One 3(5):e2141. doi: 10.1371/journal.pone.0002141 PubMedCrossRefGoogle Scholar
  74. 74.
    Zhang C, Wang C, Chen X, Yang C, Li K, Wang J, Dai J, Hu Z, Zhou X, Chen L, Zhang Y, Li Y, Qiu H, Xing J, Liang Z, Ren B, Yang C, Zen K, Zhang CY (2010) Expression profile of microRNAs in serum: a fingerprint for esophageal squamous cell carcinoma. Clin Chem 56(12):1871–1879. doi: 10.1373/clinchem.2010.147553 PubMedCrossRefGoogle Scholar
  75. 75.
    Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, Alder H, Liu CG, Oue N, Yasui W, Yoshida K, Sasaki H, Nomura S, Seto Y, Kaminishi M, Calin GA, Croce CM (2010) Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol 11(2):136–146. doi: 10.1016/S1470-2045(09)70343-2 PubMedCrossRefGoogle Scholar
  76. 76.
    Haller F, von Heydebreck A, Zhang JD, Gunawan B, Langer C, Ramadori G, Wiemann S, Sahin O (2010) Localization- and mutation-dependent microRNA (miRNA) expression signatures in gastrointestinal stromal tumours (GISTs), with a cluster of co-expressed miRNAs located at 14q32.31. J Pathol 220(1):71–86. doi: 10.1002/path.2610 PubMedCrossRefGoogle Scholar
  77. 77.
    Bandres E, Cubedo E, Agirre X, Malumbres R, Zarate R, Ramirez N, Abajo A, Navarro A, Moreno I, Monzo M, Garcia-Foncillas J (2006) Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer 5:29. doi: 10.1186/1476-4598-5-29 PubMedCrossRefGoogle Scholar
  78. 78.
    Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X (2010) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer J Int du Cancer 127(1):118–126. doi: 10.1002/ijc.25007 CrossRefGoogle Scholar
  79. 79.
    Mosakhani N, Sarhadi VK, Borze I, Karjalainen-Lindsberg ML, Sundstrom J, Ristamaki R, Osterlund P, Knuutila S (2012) MicroRNA profiling differentiates colorectal cancer according to KRAS status. Genes Chromosom Cancer 51(1):1–9. doi: 10.1002/gcc.20925 PubMedCrossRefGoogle Scholar
  80. 80.
    Luk JM, Burchard J, Zhang C, Liu AM, Wong KF, Shek FH, Lee NP, Fan ST, Poon RT, Ivanovska I, Philippar U, Cleary MA, Buser CA, Shaw PM, Lee CN, Tenen DG, Dai H, Mao M (2011) DLK1-DIO3 genomic imprinted microRNA cluster at 14q32.2 defines a stemlike subtype of hepatocellular carcinoma associated with poor survival. J Biol Chem 286(35):30706–30713. doi: 10.1074/jbc.M111.229831 PubMedCrossRefGoogle Scholar
  81. 81.
    Tryndyak VP, Ross SA, Beland FA, Pogribny IP (2009) Down-regulation of the microRNAs miR-34a, miR-127, and miR-200b in rat liver during hepatocarcinogenesis induced by a methyl-deficient diet. Mol Carcinog 48(6):479–487. doi: 10.1002/mc.20484 PubMedCrossRefGoogle Scholar
  82. 82.
    Shih KK, Qin LX, Tanner EJ, Zhou Q, Bisogna M, Dao F, Olvera N, Viale A, Barakat RR, Levine DA (2011) A microRNA survival signature (MiSS) for advanced ovarian cancer. Gynecol Oncol 121(3):444–450. doi: 10.1016/j.ygyno.2011.01.025 PubMedCrossRefGoogle Scholar
  83. 83.
    Ye G, Fu G, Cui S, Zhao S, Bernaudo S, Bai Y, Ding Y, Zhang Y, Yang BB, Peng C (2011) MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance. J Cell Sci 124(Pt 3):359–368. doi: 10.1242/jcs.072223 PubMedCrossRefGoogle Scholar
  84. 84.
    Castilla MA, Moreno-Bueno G, Romero-Perez L, Van De Vijver K, Biscuola M, Lopez-Garcia MA, Prat J, Matias-Guiu X, Cano A, Oliva E, Palacios J (2011) Micro-RNA signature of the epithelial-mesenchymal transition in endometrial carcinosarcoma. J Pathol 223(1):72–80. doi: 10.1002/path.2802 PubMedCrossRefGoogle Scholar
  85. 85.
    Lee JW, Choi CH, Choi JJ, Park YA, Kim SJ, Hwang SY, Kim WY, Kim TJ, Lee JH, Kim BG, Bae DS (2008) Altered microRNA expression in cervical carcinomas. Clin Cancer Res Off J Am Assoc Cancer Res 14(9):2535–2542. doi: 10.1158/1078-0432.CCR-07-1231 CrossRefGoogle Scholar
  86. 86.
    Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, Liu CG, Giannakakis A, Alexiou P, Hasegawa K, Johnstone CN, Megraw MS, Adams S, Lassus H, Huang J, Kaur S, Liang S, Sethupathy P, Leminen A, Simossis VA, Sandaltzopoulos R, Naomoto Y, Katsaros D, Gimotty PA, DeMichele A, Huang Q, Butzow R, Rustgi AK, Weber BL, Birrer MJ, Hatzigeorgiou AG, Croce CM, Coukos G (2008) Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci USA 105(19):7004–7009. doi: 10.1073/pnas.0801615105 PubMedCrossRefGoogle Scholar
  87. 87.
    Wang LL, Zhang Z, Li Q, Yang R, Pei X, Xu Y, Wang J, Zhou SF, Li Y (2009) Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation. Hum Reprod 24(3):562–579. doi: 10.1093/humrep/den439 PubMedCrossRefGoogle Scholar
  88. 88.
    Tang H, Liu X, Wang Z, She X, Zeng X, Deng M, Liao Q, Guo X, Wang R, Li X, Zeng F, Wu M, Li G (2011) Interaction of hsa-miR-381 and glioma suppressor LRRC4 is involved in glioma growth. Brain Res 1390:21–32. doi: 10.1016/j.brainres.2011.03.034 PubMedCrossRefGoogle Scholar
  89. 89.
    Swarbrick A, Woods SL, Shaw A, Balakrishnan A, Phua Y, Nguyen A, Chanthery Y, Lim L, Ashton LJ, Judson RL, Huskey N, Blelloch R, Haber M, Norris MD, Lengyel P, Hackett CS, Preiss T, Chetcuti A, Sullivan CS, Marcusson EG, Weiss W, L’Etoile N, Goga A (2010) miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma. Nat Med 16(10):1134–1140. doi: 10.1038/nm.2227 PubMedCrossRefGoogle Scholar
  90. 90.
    Skalsky RL, Cullen BR (2011) Reduced expression of brain-enriched microRNAs in glioblastomas permits targeted regulation of a cell death gene. PLoS One 6(9):e24248. doi: 10.1371/journal.pone.0024248 PubMedCrossRefGoogle Scholar
  91. 91.
    Gattolliat CH, Thomas L, Ciafre SA, Meurice G, Le Teuff G, Job B, Richon C, Combaret V, Dessen P, Valteau-Couanet D, May E, Busson P, Douc-Rasy S, Benard J (2011) Expression of miR-487b and miR-410 encoded by 14q32.31 locus is a prognostic marker in neuroblastoma. Br J Cancer 105(9):1352–1361. doi: 10.1038/bjc.2011.388 PubMedCrossRefGoogle Scholar
  92. 92.
    Cheunsuchon P, Zhou Y, Zhang X, Lee H, Chen W, Nakayama Y, Rice KA, Tessa Hedley-Whyte E, Swearingen B, Klibanski A (2011) Silencing of the imprinted DLK1-MEG3 locus in human clinically nonfunctioning pituitary adenomas. Am J Pathol 179(4):2120–2130. doi: 10.1016/j.ajpath.2011.07.002 PubMedCrossRefGoogle Scholar
  93. 93.
    Liu L, Jiang Y, Zhang H, Greenlee AR, Han Z (2010) Overexpressed miR-494 down-regulates PTEN gene expression in cells transformed by anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide. Life Sci 86(5–6):192–198. doi: 10.1016/j.lfs.2009.12.002 PubMedCrossRefGoogle Scholar
  94. 94.
    Duan H, Jiang Y, Zhang H, Wu Y (2010) MiR-320 and miR-494 affect cell cycles of primary murine bronchial epithelial cells exposed to benzo[a]pyrene. Toxicol In vitro Int J publ Assoc BIBRA 24(3):928–935. doi: 10.1016/j.tiv.2009.11.013 CrossRefGoogle Scholar
  95. 95.
    Guo L, Liu Y, Bai Y, Sun Y, Xiao F, Guo Y (2010) Gene expression profiling of drug-resistant small cell lung cancer cells by combining microRNA and cDNA expression analysis. Eur J Cancer 46(9):1692–1702. doi: 10.1016/j.ejca.2010.02.043 PubMedCrossRefGoogle Scholar
  96. 96.
    Dacic S, Kelly L, Shuai Y, Nikiforova MN (2010) miRNA expression profiling of lung adenocarcinomas: correlation with mutational status. Mod Pathol Off J USA Can Acad Pathol Inc 23(12):1577–1582. doi: 10.1038/modpathol.2010.152 Google Scholar
  97. 97.
    Liu X, Sempere LF, Ouyang H, Memoli VA, Andrew AS, Luo Y, Demidenko E, Korc M, Shi W, Preis M, Dragnev KH, Li H, Direnzo J, Bak M, Freemantle SJ, Kauppinen S, Dmitrovsky E (2010) MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J Clin Investig 120(4):1298–1309. doi: 10.1172/JCI39566 PubMedCrossRefGoogle Scholar
  98. 98.
    Guled M, Lahti L, Lindholm PM, Salmenkivi K, Bagwan I, Nicholson AG, Knuutila S (2009) CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma-A miRNA microarray analysis. Genes Chromosom Cancer 48(7):615–623. doi: 10.1002/gcc.20669 PubMedCrossRefGoogle Scholar
  99. 99.
    Hwang-Verslues WW, Chang PH, Wei PC, Yang CY, Huang CK, Kuo WH, Shew JY, Chang KJ, Lee EY, Lee WH (2011) miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1. Oncogene 30(21):2463–2474. doi: 10.1038/onc.2010.618 PubMedCrossRefGoogle Scholar
  100. 100.
    Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C, Benes V, Schmidt S, Blake J, Ball G, Kerin MJ (2009) MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res BCR 11(3):R27. doi: 10.1186/bcr2257 CrossRefGoogle Scholar
  101. 101.
    Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX, Shao JY (2008) MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 14(11):2348–2360. doi: 10.1261/rna.1034808 PubMedCrossRefGoogle Scholar
  102. 102.
    Bockmeyer CL, Christgen M, Muller M, Fischer S, Ahrens P, Langer F, Kreipe H, Lehmann U (2011) MicroRNA profiles of healthy basal and luminal mammary epithelial cells are distinct and reflected in different breast cancer subtypes. Breast Cancer Res Treat 130(3):735–745. doi: 10.1007/s10549-010-1303-3 PubMedCrossRefGoogle Scholar
  103. 103.
    Kriegel AJ, Fang Y, Liu Y, Tian Z, Mladinov D, Matus IR, Ding X, Greene AS, Liang M (2010) MicroRNA-target pairs in human renal epithelial cells treated with transforming growth factor beta 1: a novel role of miR-382. Nucleic Acids Res 38(22):8338–8347. doi: 10.1093/nar/gkq718 PubMedCrossRefGoogle Scholar
  104. 104.
    Tombol Z, Eder K, Kovacs A, Szabo PM, Kulka J, Liko I, Zalatnai A, Racz G, Toth M, Patocs A, Falus A, Racz K, Igaz P (2010) MicroRNA expression profiling in benign (sporadic and hereditary) and recurring adrenal pheochromocytomas. Mod Pathol Off J USA Canad Acad Pathol Inc 23(12):1583–1595. doi: 10.1038/modpathol.2010.164 Google Scholar
  105. 105.
    Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, Jones PA (2006) Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 9(6):435–443. doi: 10.1016/j.ccr.2006.04.020 PubMedCrossRefGoogle Scholar
  106. 106.
    Nagano T, Fraser P (2011) No nonsense functions for long noncoding RNAs. Cell 145(2):178–181. doi: 10.1016/j.cell.2011.03.014 PubMedCrossRefGoogle Scholar
  107. 107.
    Bertani S, Sauer S, Bolotin E, Sauer F (2011) The noncoding RNA mistral activates Hoxa6 and Hoxa7 expression and stem cell differentiation by recruiting MLL1 to chromatin. Mol Cell 43(6):1040–1046. doi: 10.1016/j.molcel.2011.08.019 PubMedCrossRefGoogle Scholar
  108. 108.
    Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I (2006) A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes. Cell 126(6):1203–1217. doi: 10.1016/j.cell.2006.07.031 PubMedCrossRefGoogle Scholar
  109. 109.
    da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57. doi: 10.1038/nprot.2008.211 CrossRefGoogle Scholar
  110. 110.
    Robertus JL, Harms G, Blokzijl T, Booman M, de Jong D, van Imhoff G, Rosati S, Schuuring E, Kluin P, van den Berg A (2009) Specific expression of miR-17-5p and miR-127 in testicular and central nervous system diffuse large B-cell lymphoma. Mod Pathol Off J US Can Acad Pathol Inc 22(4):547–555. doi: 10.1038/modpathol.2009.10 Google Scholar
  111. 111.
    Lim PK, Bliss SA, Patel SA, Taborga M, Dave MA, Gregory LA, Greco SJ, Bryan M, Patel PS, Rameshwar P (2011) Gap junction-mediated import of microRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells. Cancer Res 71(5):1550–1560. doi: 10.1158/0008-5472.CAN-10-2372 PubMedCrossRefGoogle Scholar
  112. 112.
    Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE (2009) The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol 112(1):55–59. doi: 10.1016/j.ygyno.2008.08.036 PubMedCrossRefGoogle Scholar
  113. 113.
    Lages E, Guttin A, El Atifi M, Ramus C, Ipas H, Dupre I, Rolland D, Salon C, Godfraind C, deFraipont F, Dhobb M, Pelletier L, Wion D, Gay E, Berger F, Issartel JP (2011) MicroRNA and target protein patterns reveal physiopathological features of glioma subtypes. PLoS One 6(5):e20600. doi: 10.1371/journal.pone.0020600 PubMedCrossRefGoogle Scholar
  114. 114.
    Cahill S, Smyth P, Denning K, Flavin R, Li J, Potratz A, Guenther SM, Henfrey R, O’Leary JJ, Sheils O (2007) Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model. Mol Cancer 6:21. doi: 10.1186/1476-4598-6-21 PubMedCrossRefGoogle Scholar
  115. 115.
    Duan Z, Choy E, Harmon D, Liu X, Susa M, Mankin H, Hornicek F (2011) MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration. Mol Cancer Ther 10(8):1337–1345. doi: 10.1158/1535-7163.MCT-11-0096 PubMedCrossRefGoogle Scholar
  116. 116.
    Genovesi LA, Carter KW, Gottardo NG, Giles KM, Dallas PB (2011) Integrated analysis of miRNA and mRNA expression in childhood medulloblastoma compared with neural stem cells. PLoS One 6(9):e23935. doi: 10.1371/journal.pone.0023935 PubMedCrossRefGoogle Scholar
  117. 117.
    Cipollone F, Felicioni L, Sarzani R, Ucchino S, Spigonardo F, Mandolini C, Malatesta S, Bucci M, Mammarella C, Santovito D, de Lutiis F, Marchetti A, Mezzetti A, Buttitta F (2011) A unique microRNA signature associated with plaque instability in humans. Stroke J Cereb Circ 42(9):2556–2563. doi: 10.1161/STROKEAHA.110.597575 CrossRefGoogle Scholar
  118. 118.
    Sylvius N, Bonne G, Straatman K, Reddy T, Gant TW, Shackleton S (2011) MicroRNA expression profiling in patients with lamin A/C-associated muscular dystrophy. FASEB J Off Publ Fed Am Soc Exp Biol 25(11):3966–3978. doi: 10.1096/fj.11-182915 Google Scholar
  119. 119.
    Tsai KW, Wu CW, Hu LY, Li SC, Liao YL, Lai CH, Kao HW, Fang WL, Huang KH, Chan WC, Lin WC (2011) Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer. Int J Cancer J Int du Cancer 129(11):2600–2610. doi: 10.1002/ijc.25919 CrossRefGoogle Scholar
  120. 120.
    Hamano R, Miyata H, Yamasaki M, Kurokawa Y, Hara J, Moon JH, Nakajima K, Takiguchi S, Fujiwara Y, Mori M, Doki Y (2011) Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway. Clin Cancer Res Off J Am Assoc Cancer Res 17(9):3029–3038. doi: 10.1158/1078-0432.CCR-10-2532 CrossRefGoogle Scholar
  121. 121.
    Dai Y, Sui W, Lan H, Yan Q, Huang H, Huang Y (2009) Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients. Rheumatol Int 29(7):749–754. doi: 10.1007/s00296-008-0758-6 PubMedCrossRefGoogle Scholar
  122. 122.
    Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW, Doevendans PA, Mummery CL, Borlak J, Haverich A, Gross C, Engelhardt S, Ertl G, Bauersachs J (2007) MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation 116(3):258–267. doi: 10.1161/CIRCULATIONAHA.107.687947 PubMedCrossRefGoogle Scholar
  123. 123.
    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 PubMedCrossRefGoogle Scholar
  124. 124.
    Xiao J, Jing ZC, Ellinor PT, Liang D, Zhang H, Liu Y, Chen X, Pan L, Lyon R, Liu Y, Peng LY, Liang X, Sun Y, Popescu LM, Condorelli G, Chen YH (2011) MicroRNA-134 as a potential plasma biomarker for the diagnosis of acute pulmonary embolism. J Transl Med 9:159. doi: 10.1186/1479-5876-9-159 PubMedCrossRefGoogle Scholar
  125. 125.
    Kim TH, Kim YK, Kwon Y, Heo JH, Kang H, Kim G, An HJ (2010) Deregulation of miR-519a, 153, and 485–5p and its clinicopathological relevance in ovarian epithelial tumours. Histopathology 57(5):734–743. doi: 10.1111/j.1365-2559.2010.03686.x PubMedCrossRefGoogle Scholar
  126. 126.
    Eisenberg I, Eran A, Nishino I, Moggio M, Lamperti C, Amato AA, Lidov HG, Kang PB, North KN, Mitrani-Rosenbaum S, Flanigan KM, Neely LA, Whitney D, Beggs AH, Kohane IS, Kunkel LM (2007) Distinctive patterns of microRNA expression in primary muscular disorders. Proc Natl Acad Sci USA 104(43):17016–17021. doi: 10.1073/pnas.0708115104 PubMedCrossRefGoogle Scholar
  127. 127.
    Hoekstra M, van der Lans CA, Halvorsen B, Gullestad L, Kuiper J, Aukrust P, van Berkel TJ, Biessen EA (2010) The peripheral blood mononuclear cell microRNA signature of coronary artery disease. Biochem Biophys Res Commun 394(3):792–797. doi: 10.1016/j.bbrc.2010.03.075 PubMedCrossRefGoogle Scholar
  128. 128.
    Lehmann U, Streichert T, Otto B, Albat C, Hasemeier B, Christgen H, Schipper E, Hille U, Kreipe HH, Langer F (2010) Identification of differentially expressed microRNAs in human male breast cancer. BMC Cancer 10:109. doi: 10.1186/1471-2407-10-109 PubMedCrossRefGoogle Scholar
  129. 129.
    Zhang X, Cairns M, Rose B, O’Brien C, Shannon K, Clark J, Gamble J, Tran N (2009) Alterations in miRNA processing and expression in pleomorphic adenomas of the salivary gland. Int J Cancer J Int du Cancer 124(12):2855–2863. doi: 10.1002/ijc.24298 CrossRefGoogle Scholar
  130. 130.
    Abu-Elneel K, Liu T, Gazzaniga FS, Nishimura Y, Wall DP, Geschwind DH, Lao K, Kosik KS (2008) Heterogeneous dysregulation of microRNAs across the autism spectrum. Neurogenetics 9(3):153–161. doi: 10.1007/s10048-008-0133-5 PubMedCrossRefGoogle Scholar
  131. 131.
    Bimpaki EI, Iliopoulos D, Moraitis A, Stratakis CA (2010) MicroRNA signature in massive macronodular adrenocortical disease and implications for adrenocortical tumourigenesis. Clin Endocrinol 72(6):744–751. doi: 10.1111/j.1365-2265.2009.03725.x CrossRefGoogle Scholar
  132. 132.
    Redell JB, Liu Y, Dash PK (2009) Traumatic brain injury alters expression of hippocampal microRNAs: potential regulators of multiple pathophysiological processes. J Neurosci Res 87(6):1435–1448. doi: 10.1002/jnr.21945 PubMedCrossRefGoogle Scholar
  133. 133.
    Hussein K, von Neuhoff N, Busche G, Buhr T, Kreipe H, Bock O (2009) Opposite expression pattern of Src kinase Lyn in acute and chronic haematological malignancies. Ann Hematol 88(11):1059–1067. doi: 10.1007/s00277-009-0727-5 PubMedCrossRefGoogle Scholar
  134. 134.
    Yao Y, Suo AL, Li ZF, Liu LY, Tian T, Ni L, Zhang WG, Nan KJ, Song TS, Huang C (2009) MicroRNA profiling of human gastric cancer. Mol Med Rep 2(6):963–970. doi: 10.3892/mmr_00000199 Google Scholar
  135. 135.
    Saba R, Goodman CD, Huzarewich RL, Robertson C, Booth SA (2008) A miRNA signature of prion induced neurodegeneration. PLoS One 3(11):e3652. doi: 10.1371/journal.pone.0003652 PubMedCrossRefGoogle Scholar
  136. 136.
    Luo H, Zhang H, Zhang Z, Zhang X, Ning B, Guo J, Nie N, Liu B, Wu X (2009) Down-regulated miR-9 and miR-433 in human gastric carcinoma. J Exp Clin Cancer Res CR 28:82. doi: 10.1186/1756-9966-28-82 CrossRefGoogle Scholar
  137. 137.
    Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, Morgan DL, Postier RG, Brackett DJ, Schmittgen TD (2007) Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer J Int du Cancer 120(5):1046–1054. doi: 10.1002/ijc.22394 CrossRefGoogle Scholar
  138. 138.
    Kumar S, Kumar A, Shah PP, Rai SN, Panguluri SK, Kakar SS (2011) MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines. J Ovarian Res 4(1):17. doi: 10.1186/1757-2215-4-17 PubMedCrossRefGoogle Scholar
  139. 139.
    Iliopoulos D, Bimpaki EI, Nesterova M, Stratakis CA (2009) MicroRNA signature of primary pigmented nodular adrenocortical disease: clinical correlations and regulation of Wnt signaling. Cancer Res 69(8):3278–3282. doi: 10.1158/0008-5472.CAN-09-0155 PubMedCrossRefGoogle Scholar
  140. 140.
    Gao W, Shen H, Liu L, Xu J, Xu J, Shu Y (2011) MiR-21 overexpression in human primary squamous cell lung carcinoma is associated with poor patient prognosis. J Cancer Res Clin Oncol 137(4):557–566. doi: 10.1007/s00432-010-0918-4 PubMedCrossRefGoogle Scholar
  141. 141.
    Wang Q, Wang Y, Minto AW, Wang J, Shi Q, Li X, Quigg RJ (2008) MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy. FASEB J Off Publ Fed Am Soc Exp Biol 22(12):4126–4135. doi: 10.1096/fj.08-112326 Google Scholar
  142. 142.
    Zhu XM, Han T, Sargent IL, Yin GW, Yao YQ (2009) Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am J Obstet Gynecol 200(6):661–667. doi: 10.1016/j.ajog.2008.12.045 PubMedCrossRefGoogle Scholar
  143. 143.
    Yu J, Wang F, Yang GH, Wang FL, Ma YN, Du ZW, Zhang JW (2006) Human microRNA clusters: genomic organization and expression profile in leukemia cell lines. Biochem Biophys Res Commun 349(1):59–68. doi: 10.1016/j.bbrc.2006.07.207 PubMedCrossRefGoogle Scholar
  144. 144.
    Wang X, Ye L, Zhou Y, Liu MQ, Zhou DJ, Ho WZ (2011) Inhibition of anti-HIV microRNA expression: a mechanism for opioid-mediated enhancement of HIV infection of monocytes. Am J Pathol 178(1):41–47. doi: 10.1016/j.ajpath.2010.11.042 PubMedCrossRefGoogle Scholar
  145. 145.
    Wong TS, Liu XB, Wong BY, Ng RW, Yuen AP, Wei WI (2008) Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue. Clin Cancer Res Off J Am Assoc Cancer Res 14(9):2588–2592. doi: 10.1158/1078-0432.CCR-07-0666 CrossRefGoogle Scholar
  146. 146.
    Goodarzi HR, Abbasi A, Saffari M, Tabei MB, Noori Daloii MR (2010) MicroRNAs take part in pathophysiology and pathogenesis of male pattern baldness. Mol Biol Rep 37(6):2959–2965. doi: 10.1007/s11033-009-9862-2 PubMedCrossRefGoogle Scholar
  147. 147.
    Hummel R, Wang T, Watson DI, Michael MZ, Van der Hoek M, Haier J, Hussey DJ (2011) Chemotherapy-induced modification of microRNA expression in esophageal cancer. Oncol Rep 26(4):1011–1017. doi: 10.3892/or.2011.1381 PubMedGoogle Scholar
  148. 148.
    Lai CY, Yu SL, Hsieh MH, Chen CH, Chen HY, Wen CC, Huang YH, Hsiao PC, Hsiao CK, Liu CM, Yang PC, Hwu HG, Chen WJ (2011) MicroRNA expression aberration as potential peripheral blood biomarkers for schizophrenia. PLoS One 6(6):e21635. doi: 10.1371/journal.pone.0021635 PubMedCrossRefGoogle Scholar
  149. 149.
    Qi Y, Tu J, Cui L, Guo X, Shi Z, Li S, Shi W, Shan Y, Ge Y, Shan J, Wang H, Lu Z (2010) High-throughput sequencing of microRNAs in adenovirus type 3 infected human laryngeal epithelial cells. J Biomed Biotechnol 2010:915980. doi: 10.1155/2010/915980 PubMedCrossRefGoogle Scholar
  150. 150.
    Simon D, Laloo B, Barillot M, Barnetche T, Blanchard C, Rooryck C, Marche M, Burgelin I, Coupry I, Chassaing N, Gilbert-Dussardier B, Lacombe D, Grosset C, Arveiler B (2010) A mutation in the 3′-UTR of the HDAC6 gene abolishing the post-transcriptional regulation mediated by hsa-miR-433 is linked to a new form of dominant X-linked chondrodysplasia. Hum Mol Genet 19(10):2015–2027. doi: 10.1093/hmg/ddq083 PubMedCrossRefGoogle Scholar
  151. 151.
    Hawkins SM, Creighton CJ, Han DY, Zariff A, Anderson ML, Gunaratne PH, Matzuk MM (2011) Functional microRNA involved in endometriosis. Mol Endocrinol 25(5):821–832. doi: 10.1210/me.2010-0371 PubMedCrossRefGoogle Scholar
  152. 152.
    Melkamu T, Zhang X, Tan J, Zeng Y, Kassie F (2010) Alteration of microRNA expression in vinyl carbamate-induced mouse lung tumors and modulation by the chemopreventive agent indole-3-carbinol. Carcinogenesis 31(2):252–258. doi: 10.1093/carcin/bgp208 PubMedCrossRefGoogle Scholar
  153. 153.
    Sander S, Bullinger L, Klapproth K, Fiedler K, Kestler HA, Barth TF, Moller P, Stilgenbauer S, Pollack JR, Wirth T (2008) MYC stimulates EZH2 expression by repression of its negative regulator miR-26a. Blood 112(10):4202–4212. doi: 10.1182/blood-2008-03-147645 PubMedCrossRefGoogle Scholar
  154. 154.
    Roccaro AM, Sacco A, Chen C, Runnels J, Leleu X, Azab F, Azab AK, Jia X, Ngo HT, Melhem MR, Burwick N, Varticovski L, Novina CD, Rollins BJ, Anderson KC, Ghobrial IM (2009) MicroRNA expression in the biology, prognosis, and therapy of Waldenstrom macroglobulinemia. Blood 113(18):4391–4402. doi: 10.1182/blood-2008-09-178228 PubMedCrossRefGoogle Scholar
  155. 155.
    Montag J, Hitt R, Opitz L, Schulz-Schaeffer WJ, Hunsmann G, Motzkus D (2009) Upregulation of miRNA hsa-miR-342-3p in experimental and idiopathic prion disease. Mol Neurodegener 4:36. doi: 10.1186/1750-1326-4-36 PubMedCrossRefGoogle Scholar
  156. 156.
    Li X, Luo F, Li Q, Xu M, Feng D, Zhang G, Wu W (2011) Identification of new aberrantly expressed miRNAs in intestinal-type gastric cancer and its clinical significance. Oncol Rep 26(6):1431–1439. doi: 10.3892/or.2011.1437 PubMedGoogle Scholar

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Leonidas Benetatos
    • 1
  • Eleftheria Hatzimichael
    • 2
    • 3
    • 4
  • Eric Londin
    • 4
  • George Vartholomatos
    • 5
  • Phillipe Loher
    • 4
  • Isidore Rigoutsos
    • 4
  • Evangelos Briasoulis
    • 2
    • 3
  1. 1.Transfusion UnitGeneral Hospital of PrevezaPrevezaGreece
  2. 2.Department of HematologyUniversity Hospital of IoanninaIoanninaGreece
  3. 3.Cancer Biobank CenterUniversity of IoanninaIoanninaGreece
  4. 4.Computational Medicine Center, Jefferson Medical CollegeThomas Jefferson UniversityPhiladelphiaUSA
  5. 5.Molecular Biology LaboratoryUniversity Hospital of IoanninaIoanninaGreece

Personalised recommendations