Skip to main content
SpringerLink
Log in

MicroRNAs as biomarkers of disease onset

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are small, noncoding RNA molecules with the ability to posttranscriptionally regulate gene expression via targeting the 3′ untranslated region of messenger RNAs. miRNAs are critical for normal cellular functions such as the regulation of the cell cycle, differentiation, and apoptosis, and they target genes during embryonal and postnatal development, whereas their expression is unbalanced in various pathological states. Importantly, miRNAs are abundantly present in body fluids (e.g., blood), which are routinely examined in patients. These molecules circulate in free and exosome encapsulated forms, and can be efficiently detected and amplified by means of molecular biology tools such as real-time PCR. Together with relative stability, specificity, and reproducibility, they are seen as good candidates for early recognition of the onset of disease. Thus, miRNAs might be considered as biomarkers for many pathological states.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Lee RC, Feinbaum RL, Ambros V (1993) Cell 75(5):843–854

    Article  CAS  Google Scholar 

  2. Vasudevan S, Tong Y, Steitz JA (2007) Science 318(5858):1931–1934

    Article  CAS  Google Scholar 

  3. Lo YM, Chiu RW (2009) Clin Chem 55(4):607–608

    Article  CAS  Google Scholar 

  4. Alvarez- Garcia L, Miska E (2005) Development 132(21):4653–4662

  5. Bartel DP (2009) Cell 136(2):215–233

    Article  CAS  Google Scholar 

  6. Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foà R, Schliwka J, Fuchs U, Novosel A, Müller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, Choksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T (2007) Cell 129(7):1401–1414

    Article  CAS  Google Scholar 

  7. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Proc Natl Acad Sci USA 105(30):10513–10518

    Article  CAS  Google Scholar 

  8. Patnaik SK, Mallick R, Yendamuri S (2010) Anal Biochem 407(1):147–149

    Article  CAS  Google Scholar 

  9. Ullah MF, Aatif M (2009) Cancer Treat Rev 35(3):193–200

    Article  Google Scholar 

  10. Shi M, Guo N (2009) Cancer Treat Rev 35(4):328–334

    Article  CAS  Google Scholar 

  11. 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) Nature 435(7043):834–838

    Article  CAS  Google Scholar 

  12. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ (2004) Science 305(5689):1437–1441

    Article  CAS  Google Scholar 

  13. Yin JQ (2009) Trends Biotechnol 26(2):70–76

    Article  CAS  Google Scholar 

  14. Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J, Di Padova F, Lin SC, Gram H, Han J (2005) Cell 120:623–634

    Article  CAS  Google Scholar 

  15. Qavi AJ, Kindt JT, Bailey RC (2010) Anal Bioanal Chem 398(6):2535–2549

    Article  CAS  Google Scholar 

  16. Várallyay E, Burgyán J, Havelda Z (2004) Nat Protoc 3(2):190–196

    Article  CAS  Google Scholar 

  17. Válóczi A, Hornyik C, Varga N, Burgyán J, Kauppinen S, Havelda Z (2004) Nucleic Acids Res 32(22):e175

    Article  CAS  Google Scholar 

  18. Lakshmipathy U, Love B, Adams C, Thyagarajan B, Chesnut JD (2007) Meth Mol Biol 407:97–114

    Article  CAS  Google Scholar 

  19. Kumar P, Johnston BH, Kazakov SA (2011) RNA 17(2):365–380

    Article  CAS  Google Scholar 

  20. Klee EW (2008) Clin Lab Med 28(1):127–143, viii

    Article  Google Scholar 

  21. Vistnes M, Christensen G, Omland T (2010) Expert Rev Mol Diagn 10(2):147–157

    Article  CAS  Google Scholar 

  22. Becker G (2002) J Neurol 249(Suppl 3):III/40-48

  23. Wild E, Bjorqkvist M, Tabrizi S (2008) Expert Rev Neurother 8(12):1779–1781

    Article  Google Scholar 

  24. Qi J, Yu JY, Shcherbata HR, Mathieu J, Wang AJ, Seal S, Zhou W, Stadler BM, Bourgin D, Wang L, Nelson A, Ware C, Raymond C, Lim LP, Magnus J, Ivanovska I, Diaz R, Ball A, Cleary MA, Ruohola-Baker H (2009) Cell Cycle 8(22):3729–3741

    Article  CAS  Google Scholar 

  25. Inui M, Martello G, Piccolo S (2010) Nat Rev Mol Cell Biol 11(4):252–263

    CAS  Google Scholar 

  26. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, Galas DJ, Wang K (2010) Clin Chem 56(11):1733–1741

    Article  CAS  Google Scholar 

  27. Paranjape T, Slack FJ, Weidhaas JB (2009) Gut 58(11):1546–1554

    Article  CAS  Google Scholar 

  28. Chi SW, Zang JB, Mele A, Darnell RB (2009) Nature 460(7254):479–486

    CAS  Google Scholar 

  29. Mendell JT (2008) Cell 133(2):217–222

    Article  CAS  Google Scholar 

  30. Croce CM, Calin GA (2005) Cell 122(1):6–7

    Article  CAS  Google Scholar 

  31. Wang B, Majumder S, Nuovo G, Kutay H, Volinia S, Patel T, Schmittgen TD, Croce C, Ghoshal K, Jacob ST (2009) Hepatology 50(4):1152–1161

    Article  CAS  Google Scholar 

  32. Gaughwin P, Ciesla M, Lahiri N, Tabrizi S, Brundin P, Bjorqkvist M (2011) Hum Mol Gen (accepted)

  33. Wang WX, Rajeev BW, Stromberg AJ, Ren N, Tang G, Huang Q, Rigoutsos I, Nelson PT (2008) J Neurosci 28(5):1213–1223

    Article  CAS  Google Scholar 

  34. Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee ML, Schmittgen TD, Nana-Sinkam SP, Jarjoura D, Marsh CB (2008) PLoS ONE 3(11):e3694

    Article  CAS  Google Scholar 

  35. Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, Ratajczak MZ (2006) Leukemia 20:847–856

    Article  CAS  Google Scholar 

  36. Wieckowski E, Whiteside TL (2006) Immunol Res 36:247–254

    Article  CAS  Google Scholar 

  37. Valenti R, Huber V, Iero M, Filipazzi P, Parmiani G, Rivoltini L (2007) Cancer Res 67:2912–2915

    Article  CAS  Google Scholar 

  38. Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ (2006) Leukemia 20:1487–1495

    Article  CAS  Google Scholar 

  39. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007) Nat Cell Biol 9:654–659

    Article  CAS  Google Scholar 

  40. Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J, Ratajczak MZ (2005) Int J Cancer 113:752–760

    Article  CAS  Google Scholar 

  41. Janiszewski M (2004) Do Carmo AO, Pedro MA, Silva E, Knobel E, Laurindo FR. Crit Care Med 32:818–825

    Article  CAS  Google Scholar 

  42. Meziani F, Tesse A, Andriantsitohaina R (2008) Pharmacol Rep 60:75–84

    CAS  Google Scholar 

  43. Cho WC (2007) Mol Cancer 6:60

    Article  CAS  Google Scholar 

  44. Manikandan J, Aarthi JJ, Kumar SD, Pushparaj PN (2008) Bioinformation 2(8):330–334

    Google Scholar 

  45. Luedde T (2010) Hepatology 52(3):1164–1166

    Article  Google Scholar 

  46. Xia W, Li J, Chen L, Huang B, Li S, Yang G, Ding H, Wang F, Liu N, Zhao Q, Fang T, Song T, Wang T, Shao N (2010) Mol Cell Biochem 344(1–2):261–266

    Article  CAS  Google Scholar 

  47. Glinskii AB (2009) Cell Cycle 8(23):3925–3942

    Article  CAS  Google Scholar 

  48. Yazici H, Zipprich J, Peng T, Akisik EZ, Tigli H, Isin M, Akisik EE, Terry MB, Senie RT, Li L, Peng M, Liu Z, Dalay N, Santella RM (2009) J Oncol 2009:827532

    Google Scholar 

  49. Lin J, Horikawa Y, Tamboli P, Clague J, Wood CG, Wu X (2010) Carcinogenesis 31(10):1805–1812

    Article  CAS  Google Scholar 

  50. Subramanian S, Steer CJ (2010) J Cell Physiol 223(2):289–298

    CAS  Google Scholar 

  51. Ladeiro Y, Couchy G, Balabaud C, Bioulac-Sage P, Pelletier L, Rebouissou S, Zucman-Rossi J (2008) Hepatology 47(6):1955–1963

    Article  CAS  Google Scholar 

  52. Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D (2008) Dev Cell 15(2):272–284

    Article  CAS  Google Scholar 

  53. Kuhnert F, Mancuso MR, Hampton J, Stankunas K, Asano T, Chen CZ, Kuo CJ (2008) Development 135(24):3989–3993

    Article  CAS  Google Scholar 

  54. Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R, Olson EN (2008) Dev Cell 15(2):261–271

    Article  CAS  Google Scholar 

  55. Fisch JE, Srivastava D (2009) Sci Signal 6:2(52):pe1

    Google Scholar 

  56. 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) Nature 435(7043):828–833

    Article  CAS  Google Scholar 

  57. Dews M, Fox JL, Hultine S, Sundaram P, Wang W, Liu YY, Furth E, Enders GH, El-Deiry W, Schelter JM, Cleary MA, Thomas-Tikhonenko A (2010) Cancer Res 70(20):8233–8246

    Article  CAS  Google Scholar 

  58. Urbich C, Kuehbacher A, Dimmeler S (2008) Cardiovasc Res 79(4):581–588

    Article  CAS  Google Scholar 

  59. Chen Y, Gorski DH (2008) Blood 111:1217–1226

    Article  CAS  Google Scholar 

  60. Crosby ME, Devlin CM, Glazer PM, Calin GA, Ivan M (2009) Curr Pharm Des 15(33):3861–3866

    Article  CAS  Google Scholar 

  61. Lee DY, Deng Z, Wang CH, Yang BB (2007) Proc Natl Acad Sci USA 104(51):20350–20355

    Article  CAS  Google Scholar 

  62. Finnerty JR, Wang WX, Hébert SS, Wilfred BR, Mao G, Nelson PT (2010) J Mol Biol 402(3):491–509

    Article  CAS  Google Scholar 

  63. Wang S, Olson EN (2009) Curr Opin Genet Dev 19(3):205–11

    Article  CAS  Google Scholar 

  64. Li Q, Wang G, Shan JL, Yang ZX, Wang HZ, Feng J, Zhen JJ, Chen C, Zhang ZM, Xu W, Luo XZ, Wang D (2010) J Gastroenterol Hepatol 25(1):164–171

    Article  CAS  Google Scholar 

  65. Heneghan HM, Miller N, Kelly R, Newell J, Kerin MJ (2010) Oncologist 15(7):673–682

    Article  Google Scholar 

  66. Zhang XJ, Ye H, Zeng CW, He B, Zhang H, Chen YQ (2010) J Hematol Oncol 3:46

    Article  CAS  Google Scholar 

  67. Doebele C, Bonauer A, Fischer A, Scholz A, Reiss Y, Urbich C, Hofmann WK, Zeiher AM, Dimmeler S (2010) Blood 115(23):4944–4950

    Article  CAS  Google Scholar 

  68. Kuhnert F, Kuo CJ (2010) Blood 115(23):4631–4633

    Article  CAS  Google Scholar 

  69. Benameur T, Soleti R, Porro C, Andriantsitohaina R, Martínez MC (2010) PLoS ONE 5(9):e12688

    Article  CAS  Google Scholar 

  70. Bonauer A, Boon RA, Dimmeler S (2010) Curr Drug Targets 11(8):943–949

    Article  CAS  Google Scholar 

  71. Esquela-Kerscher A, Slack F (2006) Nat Rev Cancer 6(4):259–269

    Article  CAS  Google Scholar 

  72. Rachakonda V, Pan TH, Le WD (2004) Cell Res 14(5):347–358

    Article  CAS  Google Scholar 

  73. Tabrizi SJ, Langbehn DR, Leavitt BR, Roos RA, Durr A, Craufurd D, Kennard C, Hicks SL, Fox NC, Scahill RI, Borowsky B, Tobin AJ, Rosas HD, Johnson H, Reilmann R, Landwehrmeyer B, Stout JC (2009) Lancet Neurol 8:791–801

    Article  Google Scholar 

  74. Sassone J, Colciago C, Cislaghi G, Silani V, Ciammola A (2009) Exp Neurol 219:385–397

    Article  CAS  Google Scholar 

  75. Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Ensen RV, Krainc D (2005) Proc Natl Acad Sci USA 102(31):11023–11028

    Article  CAS  Google Scholar 

  76. Schratt G (2009) Nat Rev Neurosci 10(12):842–849

    Article  CAS  Google Scholar 

  77. Barmack NH, Qian Z, Yakhnitsa V (2010) Neuroscience 171(3):655–665

    Article  CAS  Google Scholar 

  78. Cogswell JP, Ward J, Taylor IA, Waters M, Shi Y, Cannon B, Kelnar K, Kemppainen J, Brown D, Chen C, Prinjha RK, Richardson JC, Saunders AM, Roses AD, Richards CA (2008) J Alzheimers Dis 14(1):27–41

    CAS  Google Scholar 

  79. Caraci F, Battaglia G, Bruno V, Bosco P, Carbonaro V, Giuffrida ML, Drago F, Sortino MA, Nicoletti F, Copani A (2009) CNS Neurosci Ther

  80. Wang H, Liu J, Zong Y, Xu Y, Deng W, Zhu H, Liu Y, Ma C, Huang L, Zhang L, Qin C (2010) Brain Res 1357:166–174

    Article  CAS  Google Scholar 

  81. Liu N, Olson EN (2010) Dev Cell 18(4):510–525

    Article  CAS  Google Scholar 

  82. Port JD, Sucharov C (2010) J Cardiovasc Pharmacol 56(5):444–453

    Article  CAS  Google Scholar 

  83. Kartha RV, Subramanian S (2010) J Cardiovasc Transl Res 3(3):256–270

    Article  Google Scholar 

  84. Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D (2009) Nature 460(7256):705–710

    CAS  Google Scholar 

  85. Port JD, Sucharov C (2010) J Cardiovasc Pharmacol 56(5):444–453

    Article  CAS  Google Scholar 

  86. McCarthy JJ (2008) Biochim Biophys Acta 1779(11):682–691

    CAS  Google Scholar 

  87. Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ (2006) Nat Genet 38(2):228–233

    Article  CAS  Google Scholar 

  88. Kuwahara K, Teg Pipes GC, McAnally J, Richardson JA, Hill JA, Bassel-Duby R, Olson EN (2007) J Clin Invest 117(5):1324–1334

    Article  CAS  Google Scholar 

  89. Kim HK, Lee YS, Sivaprasad U, Malhotra A, Dutta A (2006) J Cell Biol 174(5):677–687

    Article  CAS  Google Scholar 

  90. Simon DJ, Madison JM, Conery AL, Thompson-Peer KL, Soskis M, Ruvkun GB, Kaplan JM, Kim JK (2008) Cell 133(5):903–915

    Article  CAS  Google Scholar 

  91. Nebbioso A, Manzo F, Miceli M, Conte M, Manente L, Baldi A, De Luca A, Rotili D, Valente S, Mai A, Usiello A, Gronemeyer H, Altucci L (2009) EMBO Rep 10(7):776–782

    Article  CAS  Google Scholar 

  92. Takaya T, Ono K, Kawamura T, Takanabe R, Kaichi S, Morimoto T, Wada H, Kita T, Shimatsu A, Hasegawa K (2009) Circ J 73(8):1492–1497

    Article  CAS  Google Scholar 

  93. D'Alessandra Y, Devanna P, Limana F, Straino S, Di Carlo A, Brambilla PG, Rubino M, Carena MC, Spazzafumo L, De Simone M, Micheli B, Biglioli P, Achilli F, Martelli F, Maggiolini S, Marenzi G, Pompilio G, Capogrossi MC (2010) Eur Heart J 31(22):2765–2673

    Article  CAS  Google Scholar 

  94. White HD, Chew DP (2008) Lancet 372(9638):570–584

    Article  CAS  Google Scholar 

  95. Adachi T, Nakanishi M, Otsuka Y, Nishimura K, Hirokawa G, Goto Y, Nonogi H, Iwai N (2010) Clin Chem 56(7):1183–1185

    Article  CAS  Google Scholar 

  96. Frost RJ, van Rooij E (2010) J Cardiovasc Transl Res 3(3):280–289

    Article  Google Scholar 

  97. Plaisance V, Abderrahmani A, Perret-Menoud V, Jacquemin P, Lemaigre F, Regazzi R (2006) J Biol Chem 281(37):26932–26942

    Article  CAS  Google Scholar 

  98. Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M (2010) Circ Res 107(6):810–817

    Article  CAS  Google Scholar 

  99. Zou J, Li WQ, Li Q, Li XQ, Zhang JT, Liu GQ, Chen J, Qiu XX, Tian FJ, Wang ZZ, Zhu N, Qin YW, Shen B, Liu TX, Jing Q (2010) Circ Res

  100. Morrisey EE (2010) J Clin Invest 120(11):3817–3819

    Article  CAS  Google Scholar 

  101. Chen J, Yang T, Yu H, Sun K, Shi Y, Song W, Bai Y, Wang X, Lou K, Song Y, Zhang Y, Hui R (2010) Hum Mol Genet 19(12):2524–2533

    Article  CAS  Google Scholar 

  102. Puisségur MP, Mazure NM, Bertero T, Pradelli L, Grosso S, Robbe-Sermesant K, Maurin T, Lebrigand K, Cardinaud B, Hofman V,´Fourre S, Magnone V, Ricci JE, Pouysségur J, Gounon P, Hofman P, Barbry P, Mari B (2010) Cell Death Differ

  103. Nelson PT, Wang WX (2010) J Alzheimers Dis 21(1):75–79

    CAS  Google Scholar 

  104. Packer AN, Xing Y, Harper SQ, Jones L, Davidson BL (2008) J Neurosci 28(53):14341–14346

    Article  CAS  Google Scholar 

  105. Williams AH, Valdez G, Moresi V, Qi X, McAnally J, Elliott JL, Bassel-Duby R, Sanes JR, Olson EN (2009) Science 326(5959):1549–1554

    Article  CAS  Google Scholar 

  106. Wang JF, Yu ML, Yu G, Bian JJ, Deng XM, Wan XJ, Zhu KM (2010) Biochem Biophys Res Commun 394(1):184–188

    Article  CAS  Google Scholar 

  107. Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, Asahara H (2008) Arthritis Rheum 58(5):1284–1292

    Article  CAS  Google Scholar 

  108. Divekar AA, Dubey S, Gangalum PR, Singh RR (2011) J Immunol 186:924–930

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the grants DWM/N148/INCA/08 and 311/N-COST/2008, statutory funds from the Polish Ministry of Science and Higher Education, and by Ph.D. grant from Adamed Ltd. A.J. is a recipient of a Wellcome Trust Senior Research Fellowship in Basic Biomedical Science. A.L. is a recipient of a Fellowship for Young Scientists funded by the Ministry of Science and Higher Education. The Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University is a beneficiary of structural funds from the European Union (grants POIG.02.01.00-12-064/08, 02.02.00-00-014/08, 01.0102-00-109/09, and 01.01.02-00-069/09). The Department of Medical Biotechnology participates in the COST CM0602 (ANGIOKEM) and TD0901 (HypoxiaNet) Actions, both supported by the European Commission.

Author information

Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30–387, Kraków, Poland

    Maciej Ciesla, Klaudia Skrzypek, Magdalena Kozakowska, Agnieszka Loboda, Alicja Jozkowicz & Jozef Dulak

Authors
  1. Maciej Ciesla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaudia Skrzypek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Magdalena Kozakowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Agnieszka Loboda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alicja Jozkowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jozef Dulak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jozef Dulak.

Additional information

Published in the special issue Biomarkers with Guest Editors Boguslaw Buszewski and Jochen Schubert.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ciesla, M., Skrzypek, K., Kozakowska, M. et al. MicroRNAs as biomarkers of disease onset. Anal Bioanal Chem 401, 2051–2061 (2011). https://doi.org/10.1007/s00216-011-5001-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-011-5001-8

Keywords

Search

Navigation