Skip to main content

Advertisement

Log in

Expression of the ribonucleases Drosha, Dicer, and Ago2 in colorectal carcinomas

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The pathogenesis of colorectal carcinoma (CRC) is a complex process that involves the recruitment of both genetic and epigenetic mechanisms. Recent studies underline the cardinal role of small, noncoding RNA molecules, called microRNAs (miRs), in the pathobiology of numerous physiological and pathological processes, including oncogenesis. MiR biogenesis and maturation is mainly regulated by the nuclear ribonuclease Drosha and the cytoplasmic ribonucleases Dicer and Ago2. In the present study, we investigated the expression and distribution of these molecules in three colon cancer cell lines and in human CRC samples. Drosha, Dicer, and Ago2 mRNA and protein expression was assessed with real-time PCR, western blotting, and immunofluorescence. Our experiments showed that Drosha, Dicer, and Ago2 were expressed in all the cell lines and in the majority of the CRC samples examined. The mRNA levels of Dicer were significantly augmented in stage III compared to stage II tumors. Our results suggest that Drosha, Dicer, and Ago2 are possibly implicated in CRC pathobiology and that Dicer might have a role in the progression of these tumors to advanced stages.

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

Access this article

Subscribe and save

Springer+ Basic
€32.70 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Vietnam)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Potter JD (1999) Colorectal cancer: molecules and populations. J Natl Cancer Inst 91:916–932

    Article  PubMed  CAS  Google Scholar 

  2. Grade M, Becker H, Liersch T, Ried T, Ghadimi BM (2006) Molecular cytogenetics: genomic imbalances in colorectal cancer and their clinical impact. Cell Oncol 28:71–84

    PubMed  CAS  Google Scholar 

  3. Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136:642–655

    Article  PubMed  CAS  Google Scholar 

  4. Ambros V (2009) The functions of animal microRNAs. Nature 431:343–349

    Google Scholar 

  5. Drakaki A, Iliopoulos D (2009) MicroRNA gene networks in oncogenesis. Curr Genomics 10:35–41

    Article  PubMed  CAS  Google Scholar 

  6. Gregory RI, Shiekhattar R (2005) MicroRNA biogenesis and cancer. Cancer Res 65:3509–3512

    Article  PubMed  CAS  Google Scholar 

  7. Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704–714

    Article  PubMed  CAS  Google Scholar 

  8. Meister G, Tuschl T (2004) Mechanisms of gene silencing by double-stranded RNA. Nature 431:343–349

    Article  PubMed  CAS  Google Scholar 

  9. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 103:2257–22561

    Article  PubMed  CAS  Google Scholar 

  10. Schepeler T, Reinert JT, Ostenfeld MS, Christensen LL, Silahtaroglu AN, Dyrskjøt L, Wiuf C, Sørensen FJ, Kruhøffer M, Laurberg S, Kauppinen S, Ørntoft TF, Andersen CL (2008) Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res 68:6416–6424

    Article  PubMed  CAS  Google Scholar 

  11. Chiosea S, Jelezcova E, Chandran U, Luo J, Mantha G, Sobol RW, Dacic S (2007) Overexpression of Dicer in precursor lesions of lung adenocarcinoma. Cancer Res 67:2345–2350

    Article  PubMed  CAS  Google Scholar 

  12. Grelier G, Voirin N, Ay AS, Cox DG, Chabaud S, Treilleux I, Léon-Goddard S, Rimokh R, Mikaelian I, Venoux C, Puisieux A, Lasset C, Moyret-Lalle (2009) Prognostic value of Dicer in human breast cancers and association with the mesenchymal phenotype. Br J Cancer 101:673–683

    Article  PubMed  CAS  Google Scholar 

  13. Merritt WM, Lin YG, Han LY, Kamat AA, Spannuth WA, Schmandt R, Urbauer D, Pennacchio LA, Cheng JF, Nick AM, Deavers MT, Mourad-Zeidan A, Wang H, Mueller P, Lenburg ME, Gray JW, Mok S, Birrer MJ, Lopez-Berestein G, Coleman RL, Bar-Eli M, Sood AK (2008) Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med 359:2641–2650

    Article  PubMed  CAS  Google Scholar 

  14. Flavin RJ, Smyth PC, Finn SP, Laios A, O'Toole SA, Barrett C, Ring M, Denning KM, Li J, Aherne ST, Aziz NA, Alhadi A, Sheppard BL, Loda M, Martin C, Sheils OM, O'Leary JJ (2008) Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients. Mod Pathol 21:676–684

    Article  PubMed  CAS  Google Scholar 

  15. Chiosea S, Jelezcova E, Chandran U, Acquafondata M, McHale T, Sobol RW, Dhir R (2006) Up-regulation of Dicer, a component of the microRNA machinery, in prostate adenocarcinoma. Am J Pathol 169:1812–1820

    Article  PubMed  CAS  Google Scholar 

  16. Chiosea SI, Barnes EL, Lai SY, Egloff AM, Sargent RL, Hunt JL, Seethala RR (2008) Mucoepidermoid carcinoma of upper aerodigestive tract: clinicopathologic study of 78 cases with immunohistochemical analysis of dicer expression. Virchows Arch 452:629–635

    Article  PubMed  CAS  Google Scholar 

  17. 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 124:2855–2863

    Article  PubMed  CAS  Google Scholar 

  18. Faber C, Horst D, Hlubek F, Kirchner T (2011) Overexpression of Dicer predicts poor survival in colorectal cancer. Eur J Cancer 47(9):1414–1419

    Article  PubMed  CAS  Google Scholar 

  19. McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) REporting recommendations for tumor MARKer prognostic studies (REMARK). Nat Clin Pract Urol 2:416–422

    Article  PubMed  CAS  Google Scholar 

  20. Papachristou DJ, Goodman MA, Cieply K, Hunt JL, Rao UN (2006) Comparison of allelic losses in chondroblastoma and primary chondrosarcoma of bone and correlation with fluorescence in situ hybridization analysis. Hum Pathol 37:890–898

    Article  PubMed  CAS  Google Scholar 

  21. Antonacopoulou AG, Tsamandas AC, Petsas T, Liava A, Scopa CD, Papavassiliou AG, Kalofonos HP (2008) EGFR, HER-2 and COX-2 levels in colorectal cancer. Histopathology 53:698–706

    Article  PubMed  CAS  Google Scholar 

  22. Vermeulen J, De Preter K, Lefever S, Nuytens J, De Vloed F, Derveaux S, Hellemans J, Speleman VJ (2011) Measurable impact of RNA quality on gene expression results from quantitative PCR. Nucleic Acid Res 39(9):e63

    Article  PubMed  CAS  Google Scholar 

  23. Hamilton SR, Vogelastein B, Kude S, Riboli E, Nakamura S, Hainaut P, Rubio CA, Sobin LH, Fogt F, Winawer SJ, Goldgar DE, Jass JR (2000) Carcinoma of the colon and rectum. In: Hamilton SR, Aaltonen LA (eds) Pathology and genetics: tumors of the digestive system. IARC Press, Lyon, pp 104–119

    Google Scholar 

  24. Slaby O, Svoboda M, Michalek J, Vyzula R (2009) MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer 28:102

    Article  Google Scholar 

  25. Dedes KJ, Natrajan R, Lambros MB, Geyer FC, Lopez-Garcia MA, Savage K, Jones RL, Reis-Filho JS (2010) Down-regulation of the miRNA master regulators Drosha and Dicer is associated with specific subgroups of breast cancer. Eur J Cancer 47:138–150

    Article  PubMed  Google Scholar 

  26. Tang X, Zhang Y, Tucker L, Ramratnam B (2010) Phosphorylation of the RNase III enzyme Drosha at Serine300 or Serine302 is required for its nuclear localization. Nucleic Acids Res 38:6610–6619

    Article  PubMed  CAS  Google Scholar 

  27. Potenza N, Papa U, Russo A (2009) Differential expression of Dicer and Argonaute genes during the differentiation of human neuroblastoma cells. Cell Biol Int 33:734–738

    Article  PubMed  CAS  Google Scholar 

  28. Potenza N, Papa U, Scaruffi P, Mosca N, Tonini GP, Russo A (2010) A novel splice variant of the human dicer gene is expressed in neuroblastoma cells. FEBS Lett 584:3452–3457

    Article  PubMed  CAS  Google Scholar 

  29. Faggad A, Budczies J, Tchernitsa O, Darb-Esfahani S, Sehouli J, Müller BM, Wirtz R, Chekerov R, Weichert W, Sinn B, Mucha C, Elwali NE, Schäfer R, Dietel M, Denkert C (2010) Prognostic significance of Dicer expression in ovarian cancer-link to global microRNA changes and oestrogen receptor expression. J Pathol 220:382–391

    PubMed  CAS  Google Scholar 

  30. Irvin-Wilson CV, Chaudhuri G (2005) Alternative initiation and splicing in dicer gene expression in human breast cells. Breast Cancer Res 7:R563–569

    Article  PubMed  CAS  Google Scholar 

  31. Wiesen JL, Tomasi TB (2009) Dicer is regulated by cellular stresses and interferons. Mol Immunol 46:1222–1228

    Article  PubMed  CAS  Google Scholar 

  32. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–1441

    Article  PubMed  CAS  Google Scholar 

  33. Adams BD, Claffey KP, White BA (2009) Argonaute-2 expression is regulated by epidermal growth factor receptor and mitogen-activated protein kinase signaling and correlates with a transformed phenotype in breast cancer cells. Endocrinology 150:14–23

    Article  PubMed  CAS  Google Scholar 

  34. Merritt WM, Bar-Eli M, Sood AK (2010) The dicey role of Dicer: implications for RNAi therapy. Cancer Res 70:2571–2574

    Article  PubMed  CAS  Google Scholar 

  35. Tchernitsa O, Kasajima A, Schäfer R, Kuban RJ, Ungethüm U, Györffy B, Neumann U, Simon E, Weichert W, Ebert MP, Röcken C (2010) Systematic evaluation of the miRNA-ome and its downstream effects on mRNA expression identifies gastric cancer progression. J Pathol 222:310–319

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

All authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Haralabos P. Kalofonos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Papachristou, D.J., Korpetinou, A., Giannopoulou, E. et al. Expression of the ribonucleases Drosha, Dicer, and Ago2 in colorectal carcinomas. Virchows Arch 459, 431–440 (2011). https://doi.org/10.1007/s00428-011-1119-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-011-1119-5

Keywords

Navigation