Expression of the microRNA regulators Drosha, Dicer and Ago2 in non-small cell lung carcinomas
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MicroRNAs are evolutionarily conserved non-coding components of the transcriptome that can post-transcriptionally control gene expression. Altered microRNA expression has been found to be a common feature of several cancers, including lung carcinomas. The biogenesis and maturation of microRNAs is known to be mediated by the ribonucleases Drosha, Dicer and Ago2. The purpose of the present study was to investigate the expression and distribution of Drosha, Dicer and Ago2 in human non-small cell lung carcinomas (NSCLC) and to relate the respective expression patterns to clinocopatholical features.
We used five human NSCLC-derived cell lines and primary formalin-fixed paraffin-embedded tissue samples from 83 NSCLC patients. Drosha, Dicer and Ago2 mRNA and protein expression levels, and their sub-cellular distributions, were assessed using RT-PCR, Western blotting, immunofluorescence and immunohistochemistry, respectively.
We found that Drosha, Dicer and Ago2 were expressed in all the cell lines and primary neoplastic and non-neoplastic tissue samples tested. The intensity of the immunohistochemical staining was found to be significantly lower in stage I tumors compared to normal lung tissues. Dicer expression was found to be significantly higher in stage II compared to stage I tumors, and in stage III compared to stage II and stage I tumors.
Our results point at a role of Drosha, Dicer and Ago2 in the development of NSCLC and suggest that Dicer may be implicated in the progression of these tumors to advanced stages.
KeywordsLung cancer microRNA Drosha Dicer Ago2
We would like to thank the Medical School, University of Patras, Greece, for providing the Advanced Light Microscopy facility.
Conflict of interest
The authors report no conflict of interest.
- 27.R.J. Flavin, P.C. Smyth, S.R. Finn, A. Laios, S.A. O’ Toole, C. Barrett, M. Ring, K.M. Denning, J. Li, S.T. Aherne, N.A. Aziz, A. Alhadi, B.L. Sheppard, M. Loda, C. Martin, O.M. Sheils, J.J. O’ Leary, Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients. Mod. Pathol. 21, 676–684 (2008)PubMedCrossRefGoogle Scholar
- 32.W.M. Merrit, Y.G. Lin, L.Y. Han, A.A. Karnat, W.A. Spannuth, R. Schumandt, D. Urbauer, L.A. Pennacchio, J.F. Cheng, A.M. Nick, M.T. Deavers, A. Mourad- Zeidan, H. Wang, P. Mueller, M.E. Lenburg, J.W. Gray, S. Mok, M.J. Birrer, G. Lopez-Berestein, R.L. Coleman, M. Bar-Eli, A.K. Sood, Dicer, Drosha and outcomes in patients with ovarian cancer. N. Engl. J. Med. 359, 2641–2650 (2008)CrossRefGoogle Scholar
- 33.W.D. Travis, E. Brambilla, H.K. Müller-Hermelink, C.C. Harris, Pathology and genetics of tumours of the lung, pleura, thymus and heart (IARC Press, Lyon, 2004), pp. 10–11Google Scholar
- 39.S. Volinia, G.A. Calin, C.G. Liu, S. Ambs, A. Cimmino, F. Petrocca, R. Visone, M. Iorio, C. Roldo, M. Ferracin, R.L. Prueitt, N. Yanaihara, G. Lanza, A. Scarpa, A. Vecchione, M. Negrini, C.C. Harris, C.M. Croce, A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. U. S. A. 103, 2257–2261 (2006)PubMedCentralPubMedCrossRefGoogle Scholar
- 41.M.M. Bjaanae, A.R. Halvorsen AR, S. Solberg, L. Jørgensen, T.A. Dragani, A. Galvan, F. Colombo, M. Anderlini, U. Pastorino, E. Kure, A.L. Børresen-Dale, O.T. Brustugun, A. Helland, Unique microRNA-profiles in EGFR-mutated lung adenocarcinomas. Int. J. Cancer 135, 1812–1821 (2014)CrossRefGoogle Scholar
- 43.C.V. Diaz-Garcia, A. Agudo-Lopez, C. Perez, A. Lopez-Martin, J.L. Rodriguez-Peralt, J. de Castro, A. Cortijo, M. Martinez-Villanueva, L. Iglesias, Dicer1, Drosha and miRNAs in patients with non-small cell lng cancer: implications for outcomes and histologic classification. Carcinogenesis 34, 1031–1038 (2013)PubMedCrossRefGoogle Scholar
- 44.G. Grelier, N. Voirin, A.S. Ay, D.G. Cox, S. Chabaud, I. Treilleux, S. Leon-Goddard, R. Rimokh, I. Mikaelian, C. Venoux, A. Puisieux, C. Lasset, C. Moyret-Lalle, Prognostic value of Dicer in human breast cancers and association with the mesenchymal phenotype. Br. J. Cancer 101, 673–683 (2009)PubMedCentralPubMedCrossRefGoogle Scholar