Skip to main content
Top
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Dicer and miRNA in relation to clinicopathological variables in colorectal cancer patients

Authors: Johannes Stratmann, Chao-Jie Wang, Sebastian Gnosa, Åsa Wallin, David Hinselwood, Xiao-Feng Sun, Hong Zhang

Published in: BMC Cancer | Issue 1/2011

Login to get access

Abstract

Background

Dicer is aberrantly expressed in several types of cancers. Applying real-time PCR, we detected the expression of Dicer mRNA in normal mucosa (n = 162), primary colorectal cancer (CRC) (n = 162) and liver metastasis (n = 37), and analysed the relationship between Dicer expression and clinicopathological features. We also correlated the expression of Dicer mRNA to the miRNA expression of miR-141, miR-200a, miR-200b, mir-200c and miR-429 in liver metastases.

Methods

RT-PCR and qPCR were used to analyse the Dicer expression in normal mucosa, primary tumour and liver metastasis by using the High Capacity cDNA Reverse Transcription Kit and TaqMan™® Gene Expression assays for Dicer and GAPDH. RT-PCR and qPCR were used to detect miRNA expression in liver metastases by utilizing TaqMan® MicroRNA Reverse Transcription Kit and TaqMan® miRNA Assays. Statistical analyses were performed with STATISTICA.

Results

Dicer expression in rectal cancer (3.146 ± 0.953) was higher than in colon cancer (2.703 ± 1.204, P = 0.018). Furthermore the Dicer expression was increased in primary tumours (3.146 ± 0.952) in comparison to that in normal mucosa from rectal cancer patients (2.816 ± 1.009, P = 0.034) but this is not evident in colon cancer patients. Dicer expression in liver metastases was decreased in comparison to that of either normal mucosa or primary tumour in both colon and rectal cancers (P < 0.05). Patients with a high Dicer expression in normal mucosa had a worse prognosis compared to those with a low Dicer expression, independently of gender, age, tumour site, stage and differentiation (P < 0.001, RR 3.682, 95% CI 1.749 - 7.750). In liver metastases, Dicer was positively related to miR-141 (R = 0.419, P = 0.015).

Conclusion

Dicer is up-regulated in the early development of rectal cancers. An increased expression of Dicer mRNA in normal mucosa from CRC patients is significantly related to poor survival independently of gender, age, tumour site, stage and differentiation.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gill S, Thomas RR, Goldberg RM: Review article: colorectal cancer chemotherapy. Aliment Pharmacol Ther. 2003, 18: 683-692. 10.1046/j.1365-2036.2003.01735.x.CrossRefPubMed Gill S, Thomas RR, Goldberg RM: Review article: colorectal cancer chemotherapy. Aliment Pharmacol Ther. 2003, 18: 683-692. 10.1046/j.1365-2036.2003.01735.x.CrossRefPubMed
2.
go back to reference Lynch HT, de la Chapelle A: Hereditary colorectal cancer. N Engl J Med. 2003, 348: 919-932. 10.1056/NEJMra012242.CrossRefPubMed Lynch HT, de la Chapelle A: Hereditary colorectal cancer. N Engl J Med. 2003, 348: 919-932. 10.1056/NEJMra012242.CrossRefPubMed
4.
go back to reference von Roon AC, Reese G, Teare J, Constantinides V, Darzi AW, Tekkis PP: The risk of cancer in patients with Crohn's disease. Dis Colon Rectum. 2007, 50: 839-855. 10.1007/s10350-006-0848-z.CrossRefPubMed von Roon AC, Reese G, Teare J, Constantinides V, Darzi AW, Tekkis PP: The risk of cancer in patients with Crohn's disease. Dis Colon Rectum. 2007, 50: 839-855. 10.1007/s10350-006-0848-z.CrossRefPubMed
5.
6.
go back to reference Mott JL: MicroRNAs Involved in Tumor Suppressor and Oncogene Pathways: Implications for Hepatobiliary Neoplasia. Hepatology. 2009, 50: 630-637. 10.1002/hep.23010.CrossRefPubMedPubMedCentral Mott JL: MicroRNAs Involved in Tumor Suppressor and Oncogene Pathways: Implications for Hepatobiliary Neoplasia. Hepatology. 2009, 50: 630-637. 10.1002/hep.23010.CrossRefPubMedPubMedCentral
7.
go back to reference Esquela-Kerscher A, Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006, 6: 259-269. 10.1038/nrc1840.CrossRefPubMed Esquela-Kerscher A, Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006, 6: 259-269. 10.1038/nrc1840.CrossRefPubMed
8.
go back to reference Thiery JP, Acloque H, Huang RYJ, Nieto MA: Epithelial-Mesenchymal Transitions in Development and Disease. Cell. 2009, 139: 871-890. 10.1016/j.cell.2009.11.007.CrossRefPubMed Thiery JP, Acloque H, Huang RYJ, Nieto MA: Epithelial-Mesenchymal Transitions in Development and Disease. Cell. 2009, 139: 871-890. 10.1016/j.cell.2009.11.007.CrossRefPubMed
9.
go back to reference Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, Enzo E, Guzzardo V, Rondina M, Spruce T, Parenti AR, Grazia Daidone M, Bicciato S, Piccolo S: A MicroRNA Targeting Dicer for Metastasis Control. Cell. 2010, 141: 1195-1207. 10.1016/j.cell.2010.05.017.CrossRefPubMed Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, Enzo E, Guzzardo V, Rondina M, Spruce T, Parenti AR, Grazia Daidone M, Bicciato S, Piccolo S: A MicroRNA Targeting Dicer for Metastasis Control. Cell. 2010, 141: 1195-1207. 10.1016/j.cell.2010.05.017.CrossRefPubMed
11.
go back to reference Takeshita D, Zenno S, Lee WC, Nagata K, Saigo K, Tanokura M: Homodimeric structure and double-stranded RNA cleavage activity of the C-terminal RNase III domain of human dicer. J Mol Biol. 2007, 374: 106-120. 10.1016/j.jmb.2007.08.069.CrossRefPubMed Takeshita D, Zenno S, Lee WC, Nagata K, Saigo K, Tanokura M: Homodimeric structure and double-stranded RNA cleavage activity of the C-terminal RNase III domain of human dicer. J Mol Biol. 2007, 374: 106-120. 10.1016/j.jmb.2007.08.069.CrossRefPubMed
13.
go back to reference Chiosea S, Jelezcova E, Chandran U, Luo J, Mantha G, Sobol RW, Dacic S: Overexpression of Dicer in Precursor Lesions of Lung Adenocarcinoma. Cancer Res. 2007, 67: 2345-2350. 10.1158/0008-5472.CAN-06-3533.CrossRefPubMed Chiosea S, Jelezcova E, Chandran U, Luo J, Mantha G, Sobol RW, Dacic S: Overexpression of Dicer in Precursor Lesions of Lung Adenocarcinoma. Cancer Res. 2007, 67: 2345-2350. 10.1158/0008-5472.CAN-06-3533.CrossRefPubMed
14.
go back to reference Karube Y: Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci. 2005, 96: 111-115. 10.1111/j.1349-7006.2005.00015.x.CrossRefPubMed Karube Y: Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci. 2005, 96: 111-115. 10.1111/j.1349-7006.2005.00015.x.CrossRefPubMed
15.
go back to reference Grelier G, Voirin N, Ay A-S, Cox DG, Chabaud S, Treilleux I, Léon-Goddard S, Rimokh R, Mikaelian I, Venoux C, Puisieux A, Lasset C, Moyret-Lalle C: Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype. BJC. 2009, 101: 673-683. 10.1038/sj.bjc.6605193.CrossRefPubMedPubMedCentral Grelier G, Voirin N, Ay A-S, Cox DG, Chabaud S, Treilleux I, Léon-Goddard S, Rimokh R, Mikaelian I, Venoux C, Puisieux A, Lasset C, Moyret-Lalle C: Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype. BJC. 2009, 101: 673-683. 10.1038/sj.bjc.6605193.CrossRefPubMedPubMedCentral
16.
go back to reference Pampalakis G, Diamandis EP, Katsaros D, Sotiropoulou G: Down-regulation of dicer expression in ovarian cancer tissues. Clin Biochem. 2010, 43: 324-327. 10.1016/j.clinbiochem.2009.09.014.CrossRefPubMed Pampalakis G, Diamandis EP, Katsaros D, Sotiropoulou G: Down-regulation of dicer expression in ovarian cancer tissues. Clin Biochem. 2010, 43: 324-327. 10.1016/j.clinbiochem.2009.09.014.CrossRefPubMed
17.
go back to reference 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: Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients. Mod Pathol. 2008, 21: 676-684. 10.1038/modpathol.2008.33.CrossRefPubMed 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: Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients. Mod Pathol. 2008, 21: 676-684. 10.1038/modpathol.2008.33.CrossRefPubMed
18.
go back to reference Chiosea S, Jelezcova E, Chandran U, Acquafondata M, McHale T, Sobol RW, Dhir R: Up-Regulation of Dicer, a Component of the MicroRNA Machinery, in Prostate Adenocarcinoma. AJP. 2006, 169: 1812-1820.PubMedPubMedCentral Chiosea S, Jelezcova E, Chandran U, Acquafondata M, McHale T, Sobol RW, Dhir R: Up-Regulation of Dicer, a Component of the MicroRNA Machinery, in Prostate Adenocarcinoma. AJP. 2006, 169: 1812-1820.PubMedPubMedCentral
19.
go back to reference Faber C, Horst D, Hlubek F, Kirchner T: Overexpression of Dicer predicts poor survival in colorectal cancer. Eur J Cancer. 2011, 47: 1414-1419. 10.1016/j.ejca.2011.01.006.CrossRefPubMed Faber C, Horst D, Hlubek F, Kirchner T: Overexpression of Dicer predicts poor survival in colorectal cancer. Eur J Cancer. 2011, 47: 1414-1419. 10.1016/j.ejca.2011.01.006.CrossRefPubMed
20.
go back to reference Agostini M, Pucciarelli S, Calore F, Bedin C, Enzo M, Nitti D: miRNAs in colon and rectal cancer: A consensus for their true clinical value. Clin Chim Acta. 2010, 411: 1181-1186. 10.1016/j.cca.2010.05.002.CrossRefPubMed Agostini M, Pucciarelli S, Calore F, Bedin C, Enzo M, Nitti D: miRNAs in colon and rectal cancer: A consensus for their true clinical value. Clin Chim Acta. 2010, 411: 1181-1186. 10.1016/j.cca.2010.05.002.CrossRefPubMed
21.
go back to reference Cheloufi S, Dos Santos CO, Chong MM, Hannon GJ: A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature. 2010, 465: 584-589. 10.1038/nature09092.CrossRefPubMedPubMedCentral Cheloufi S, Dos Santos CO, Chong MM, Hannon GJ: A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature. 2010, 465: 584-589. 10.1038/nature09092.CrossRefPubMedPubMedCentral
22.
go back to reference Xi Y, Formentini A, Chien M, Weir DB, Russo JJ, Ju J, Kornmann M, Ju J: Prognostic Values of microRNAs in Colorectal Cancer. Biomark Insights. 2006, 2: 113-121.PubMed Xi Y, Formentini A, Chien M, Weir DB, Russo JJ, Ju J, Kornmann M, Ju J: Prognostic Values of microRNAs in Colorectal Cancer. Biomark Insights. 2006, 2: 113-121.PubMed
23.
go back to reference Slaby O, Svoboda M, Michalek J, Vyzula R: MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer. 2009, 8: 102-10.1186/1476-4598-8-102.CrossRefPubMedPubMedCentral Slaby O, Svoboda M, Michalek J, Vyzula R: MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer. 2009, 8: 102-10.1186/1476-4598-8-102.CrossRefPubMedPubMedCentral
24.
go back to reference Wang CJ, Stratmann J, Zhou ZG, Sun XF: Suppression of microRNA-31 increases sensitivity to 5-FU at an early stage, and effect cell migration and invasion in HCT-116 colon cancer cells. BMC Cancer. 2010, 10: 616-10.1186/1471-2407-10-616.CrossRefPubMedPubMedCentral Wang CJ, Stratmann J, Zhou ZG, Sun XF: Suppression of microRNA-31 increases sensitivity to 5-FU at an early stage, and effect cell migration and invasion in HCT-116 colon cancer cells. BMC Cancer. 2010, 10: 616-10.1186/1471-2407-10-616.CrossRefPubMedPubMedCentral
26.
go back to reference Kapiteijn E, Liefers GJ, Los LC, Klein Kranenbarg E, Hermans J, Tollenaar RAEM, Moriya Y, van de Velde CJH, van Krieken JHJM: Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol. 2001, 195: 171-178. 10.1002/path.918.CrossRefPubMed Kapiteijn E, Liefers GJ, Los LC, Klein Kranenbarg E, Hermans J, Tollenaar RAEM, Moriya Y, van de Velde CJH, van Krieken JHJM: Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol. 2001, 195: 171-178. 10.1002/path.918.CrossRefPubMed
27.
go back to reference Dimberg J, Samuelsson A, Hugander A, Soderkvist P: Differential expression of cyclooxygenase 2 in human colorectal cancer. Gut. 1999, 45: 730-732. 10.1136/gut.45.5.730.CrossRefPubMedPubMedCentral Dimberg J, Samuelsson A, Hugander A, Soderkvist P: Differential expression of cyclooxygenase 2 in human colorectal cancer. Gut. 1999, 45: 730-732. 10.1136/gut.45.5.730.CrossRefPubMedPubMedCentral
28.
go back to reference Frattini M, Balestra D, Suardi S, Oggionni M, Alberici P, Radice P, Costa A, Grazia Daidone M, Leo E, Pilotti S, Bertario L, Pierotti MA: Different Genetic Features Associated with Colon and Rectal Carcinogenesis. Clin Cancer Res. 2004, 10: 4015-4021. 10.1158/1078-0432.CCR-04-0031.CrossRefPubMed Frattini M, Balestra D, Suardi S, Oggionni M, Alberici P, Radice P, Costa A, Grazia Daidone M, Leo E, Pilotti S, Bertario L, Pierotti MA: Different Genetic Features Associated with Colon and Rectal Carcinogenesis. Clin Cancer Res. 2004, 10: 4015-4021. 10.1158/1078-0432.CCR-04-0031.CrossRefPubMed
29.
go back to reference Chen LC, Hao CY, Chiu YSY, Wong P, Melnick JS, Brotman M, Moretto J, Mendes F, Smith AP, Bennington JA, Moore D, Lee NM: Alteration of gene expression in normal-appearing colon mucosa of APC min mice and human cancer patients. Cancer Res. 2004, 64: 3694-3700. 10.1158/0008-5472.CAN-03-3264.CrossRefPubMed Chen LC, Hao CY, Chiu YSY, Wong P, Melnick JS, Brotman M, Moretto J, Mendes F, Smith AP, Bennington JA, Moore D, Lee NM: Alteration of gene expression in normal-appearing colon mucosa of APC min mice and human cancer patients. Cancer Res. 2004, 64: 3694-3700. 10.1158/0008-5472.CAN-03-3264.CrossRefPubMed
30.
go back to reference Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, Brabletz T: A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008, 9: 582-589. 10.1038/embor.2008.74.CrossRefPubMedPubMedCentral Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, Brabletz T: A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008, 9: 582-589. 10.1038/embor.2008.74.CrossRefPubMedPubMedCentral
Metadata
Title
Dicer and miRNA in relation to clinicopathological variables in colorectal cancer patients
Authors
Johannes Stratmann
Chao-Jie Wang
Sebastian Gnosa
Åsa Wallin
David Hinselwood
Xiao-Feng Sun
Hong Zhang
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-345

Other articles of this Issue 1/2011

BMC Cancer 1/2011 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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