Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cellular Oncology
Published in: Cellular Oncology 4/2015

01-08-2015 | Original Paper

Expression of the microRNA regulators Drosha, Dicer and Ago2 in non-small cell lung carcinomas

Authors: E. Prodromaki, A. Korpetinou, E. Giannopoulou, E. Vlotinou, Μ. Chatziathanasiadou, N. I. Papachristou, C. D. Scopa, H. Papadaki, H. P. Kalofonos, D. J. Papachristou

Published in: Cellular Oncology | Issue 4/2015

Login to get access

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.
Literature
1.
Α. Jemal, F. Bray, M.M. Center, J. Ferlay, E. Ward, D. Forman, Global cancer statistics. CA Cancer J. Clin. 61, 69–90 (2011)PubMedCrossRef
2.
A. Koren, H. Motaln, T. Cufer, Lung cancer stem cells: a biological and clinical perspective. Cell. Oncol. 36, 265–275 (2013)CrossRef
3.
H. Peng, J. Huang, Y. Hu, Y. Wei, H. Liu, M. Huang, L. Wang, J. Wang, Associations between polymorphisms in the SYK promoter and susceptibility to sporadic colorectal cancer in a Southern Han Chinese population - a short report. Cell. Oncol. 38, 165–172 (2015)CrossRef
4.
E. Yiannakopoulou, Targeting epigenetic mechanisms and microRNAs by aspirin and other non steroidal anti-inflammatory agents—implications for cancer treatment and chemoprevention. Cell. Oncol. 37, 167–178 (2014)CrossRef
5.
B.P. Lewis, C.B. Burge, D.P. Bartel, Conserved seed pairing often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 14, 15–20 (2005)CrossRef
6.
7.
L.P. Lim, N.C. Lau, P. Garrett-Engele, A. Grimson, J.M. Schelter, J. Castle, D.P. Bartel, P.S. Linsley, J.M. Johnson, Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433, 769–773 (2005)PubMedCrossRef
8.
D.J. Papachristou, E. Sklirou, D. Corradi, C. Crassani, V. Kontogeorgakos, U.N.M. Rao, Immunohistochemical analysis of the endoribonucleases Drosha, Dicer and Ago2 in smooth muscle tumours of soft tissues. Histopathology 60, E28–E36 (2012)PubMedCrossRef
9.
M. Negrini, M.S. Nicoloso, G.A. Calin, MicroRNAs and cancer: new paradigms in molecular oncology. Curr. Opin. Cell Biol. 21, 470–479 (2009)PubMedCrossRef
10.
11.
Y. Wang, H.M. Stricker, D. Gou, L. Liu, MicroRNA: past and present. Front. Biosci. 12, 2316–2329 (2007)PubMedCrossRef
12.
Y. Lee, C. Ahn, J. Han, H. Choi, J. Kim, J. Lee, P. Provost, O. Radmark, S. Kim, V.N. Kim, The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415–419 (2003)PubMedCrossRef
13.
L. Rask, E. Balslev, R. Søkilde, E. Høgdall, H. Flyger, J. Eriksen, T. Litman, Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status. Cell. Oncol. 37, 215–227 (2014)CrossRef
14.
E. Lund, S. Guttinger, A. Calado, J.E. Dahlberg, U. Kutay, Nuclear export of microRNA precursors. Science 303, 95–98 (2004)PubMedCrossRef
15.
J. Mattes, A. Collison, P.S. Foster, Emerging role of microRNAs in disease pathogenesis and strategies for therapeutic modulation. Curr. Opin. Mol. Ther. 10, 150–157 (2008)PubMed
16.
17.
18.
L. Peters, G. Meister, Argonaute proteins: mediators of RNA silencing. Mol. Cell 26, 611–623 (2007)PubMedCrossRef
19.
Y. Karube, H. Tanaka, H. Osada, Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci. 96, 111–115 (2005)PubMedCrossRef
20.
S. Chiosea, E. Jelezcova, U. Chandran, J. Luo, G. Mantha, R.W. Sobol, S. Dacic, Overexpression of Dicer in precursor lesions of lung adenocarcinoma. Cancer Res. 67, 2345–2350 (2007)PubMedCrossRef
21.
D.J. Papachristou, A. Korpetinou, E. Giannopoulou, A.G. Antonakopoulou, H. Papadaki, P. Grivas, C.D. Scopa, H.P. Kalofonos, Expression of the ribonucleases Drosha, Dicer, and Ago2 in colorectal carcinomas. Virchows Arch. 459, 431–440 (2011)PubMedCrossRef
22.
S.M. Jafarnejad, C. Sjoestroem, M. Martinka, G. Li, Expression of the RNase III enzyme DROSHA is reduced during progression of human cutaneous melanoma. Mod. Pathol. 26, 902–910 (2013)PubMedCrossRef
23.
S.M. Khoshnaw, E.A. Rakha, T. Abdel-Fatah, C.C. Nolan, Z. Hodi, R.D. Macmillan, I.O. Ellis, A.R. Green, The MicroRNA maturation regulator Drosha is an independent predictor of outcome in breast cancer patients. Breast Cancer Res. Treat. 137, 139–153 (2013)PubMedCrossRef
24.
K.J. Dedes, R. Natrajan, M.B. Lambros, F.C. Geyer, M.A. Lopez-Garcia, K. Savage, R.L. Jones, J.S. Reis-Filho, Down-regulation of the miRNA master regulators Drosha and Dicer is associated with specific subgroups of breast cancer. Eur. J. Cancer 47, 138–150 (2011)PubMedCrossRef
25.
N. Sugito, H. Ishiguro, Y. Kuwabara, M. Kimura, A. Mitsui, H. Kurehara, T. Ando, R. Mori, N. Takashima, R. Ogawa, Y. Fujii, RNASEN regulates cell proliferation and affects survival in esophageal cancer patients. Clin. Cancer Res. 12, 7322–7328 (2006)PubMedCrossRef
26.
S. Chiosea, E. Jelezcova, U. Chandran, M. Acquafondata, T. McHale, R.W. Sobol, R. Dhir, Up-regulation of Dicer, a component of the micro RNA machinery, in prostate adenocarcinoma. Am. J. Pathol. 169, 1812–1820 (2006)PubMedCentralPubMedCrossRef
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)PubMedCrossRef
28.
C. Faber, D. Horst, F. Hlubek, T. Kirchner, Overexpression of Dicer predicts poor survival in colorectal cancer. Eur. J. Cancer 47, 1414–1419 (2011)PubMedCrossRef
29.
D.J. Papachristou, U.N.M. Rao, A. Korpetinou, E. Giannopoulou, E. Sklirou, V. Kontogeorgakos, H.P. Kalofonos, Dicer expression in sarcomas prognostic significance of dicer cellular levels in soft tissue sarcomas. Cancer Investig. 30, 172–179 (2011)CrossRef
30.
N. Potenza, U. Papa, A. Russo, Differential expression of Dicer and Argonaute genes during the differentiation of human neuroblastoma cells. Cell Biol. Int. 33, 734–738 (2009)PubMedCrossRef
31.
N. Potenza, U. Papa, P. Scaruffi, N. Mosca, G.P. Tonini, A. Russo, A novel splice variant of the human dicer gene is expressed in neuroblastoma cells. FEBS Lett. 584, 3452–3457 (2010)PubMedCrossRef
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)CrossRef
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. 10–11
34.
A.E. Williams, S.A. Moschos, M.M. Perry, P.J. Barnes, M.A. Lindsay, Maternally imprinted microRNAs are differentially expressed during mouse and human lung development. Dev. Dyn. 236, 572–580 (2007)PubMedCentralPubMedCrossRef
35.
C. Chen, H. Chen, J. Sun, P. Jr, Y. Bringas, D. Chen, W.S. Warburton, Smad1 expression and function during mouse embryonic lung branching morphogenesis. Am. J. Physiol. Lung Cell. Mol. Physiol. 288, 1033–1039 (2005)CrossRef
36.
D.B. Frank, A. Abtahi, D.J. Yamaguchi, S. Manning, Y. Shyr, A. Pozzi, H.S. Baldwin, J.E. Johnson, M.P. de Caestecker, Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic pulmonary hypertension. Circ. Res. 97, 496–504 (2005)PubMedCrossRef
37.
Y. Lu, J.M. Thomson, H.Y. Wong, S.M. Hammond, B.L. Hogan, Transgenic overexpression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev. Biol. 310, 442–453 (2007)PubMedCentralPubMedCrossRef
38.
Y. Li, E.Y. Chan, J. Li, C. Ni, X. Peng, E. Rosenzweig, T.M. Tumpey, M.G. Katze, MicroRNA expression and virulence in pandemic influenza virus-infected mice. J. Virol. 84, 3023–3032 (2010)PubMedCentralPubMedCrossRef
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)PubMedCentralPubMedCrossRef
40.
X. Tang, Y. Zhang, L. Tucker, B. Ramratnam, Phosphorylation of the RNase III enzyme Drosha at Serine 300 or Serine 302 is required for its nuclear localization. Nucleic Acids Res. 38, 6610–6619 (2010)PubMedCentralPubMedCrossRef
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)CrossRef
42.
S. Hong, H. Noh, H. Chen, R. Padia, Z.K. Pan, S.B. Su, Q. Jing, H.F. Ding, S. Huang, Signaling by p38 MAPK stimutaltes nuclear localization of the microprocessor component p68 for processing of selected primary MicroRNAs. Sci. Signal. 6, ra16 (2013)PubMedCrossRef
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)PubMedCrossRef
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)PubMedCentralPubMedCrossRef
45.
X. Zhang, P. Graves, Y. Zeng, Overexpression of human Argonaute2 inhibits cell and tumor growth. Biochim. Biophys. Acta 1830, 2553–2561 (2013)PubMedCrossRef
46.
J. Zhang, X.S. Fan, C.X. Wang, B. Liu, Q. Li, X.J. Zhou, Up-regulation of Ago2 expression in gastric carcinoma. Med. Oncol. 30, 628 (2013)PubMedCrossRef
47.
A.M. Liu, C. Zhang, J. Burchard, S.T. Fan, K.F. Wong, H. Dai, R.T. Poon, J.M. Luk, Global regulation on microRNA in hepatitis B virus-associated hepatocellular carcinoma. OMICS 15, 187–191 (2011)PubMedCrossRef
48.
B.D. Adams, K.P. Claffey, B.A. White, 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 (2009)PubMedCentralPubMedCrossRef
49.
S.H. Ahn, E.H. Jeong, T.G. Lee, S.Y. Kim, H.R. Kim, C.H. Kim, Gefitinib induces cytoplasmic translocation of the CDK inhibitor p27 and its binding to a cleaved intermediate of caspase 8 in non-small cell lung cancer cells. Cell. Oncol. 37, 377–386 (2014)CrossRef
Metadata
Title
Expression of the microRNA regulators Drosha, Dicer and Ago2 in non-small cell lung carcinomas
Authors
E. Prodromaki
A. Korpetinou
E. Giannopoulou
E. Vlotinou
Μ. Chatziathanasiadou
N. I. Papachristou
C. D. Scopa
H. Papadaki
H. P. Kalofonos
D. J. Papachristou
Publication date
01-08-2015
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 4/2015
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-015-0231-y

Other articles of this Issue 4/2015

Cellular Oncology 4/2015 Go to the issue

Original Paper

Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid

Report

RRM1 expression is associated with the outcome of gemcitabine-based treatment of non-small cell lung cancer patients–a short report

Original Paper

HAUSP regulates c-MYC expression via de-ubiquitination of TRRAP

Review

The bone marrow metastasis niche in retinoblastoma

Original Paper

Human renal carcinoma cells respond to Newcastle disease virus infection through activation of the p38 MAPK/NF-κB/IκBα pathway
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits