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Published in: Medical Oncology 2/2012

01-06-2012 | Original Paper

Downregulation of miR-195 correlates with lymph node metastasis and poor prognosis in colorectal cancer

Authors: Xueqing Wang, Jiandong Wang, Henghui Ma, Jin Zhang, Xiaojun Zhou

Published in: Medical Oncology | Issue 2/2012

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Abstract

miR-195, one of the miR-16/15/195/424/497 family members, has been shown to play an important role in tumorigenesis, as a tumor suppressor. Here, we assess miR-195 expression in colorectal cancer, which has not been investigated before, and its clinical significance including survival analysis. The in vivo significance of expression of miR-16/15/195/424/497 in matched normal and tumor tissues of colorectal cancers was evaluated using a quantitative real-time RT-PCR. Two colorectal cancer cell lines and 85 colorectal cancer and paired normal patient samples with detailed clinical follow-up information were selected. The statistical significance of these markers for disease prognosis was evaluated using a two-tailed, paired Wilcoxon test. A Kaplan–Meier survival curve was generated following a logrank test. As a result, miR-424 was significantly over-expressed, while miR-15a, miR-15b, miR-16, and miR-195 were downregulated in tumors compared with normal colorectal samples (all P < 0.01). Reduced expression of miR-195 occurred more often in patients with lymph node metastasis and advanced tumor stage (all P < 0.01). Kaplan–Meier survival analysis indicated that patients with reduced miR-195 had a poor overall survival (P < 0.01). Moreover, the multivariate analysis showed that reduced expression of miR-195 was an independent predictor of overall survival. Our data indicate the potential of miR-195 as a novel diagnostic or prognostic biomarker for CRC.
Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94:153–6.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94:153–6.PubMedCrossRef
2.
go back to reference Ahmed MA, et al. CD24 shows early upregulation and nuclear expression but is not a prognostic marker in colorectal cancer. J Clin Pathol. 2009;62:1117–22.PubMedCrossRef Ahmed MA, et al. CD24 shows early upregulation and nuclear expression but is not a prognostic marker in colorectal cancer. J Clin Pathol. 2009;62:1117–22.PubMedCrossRef
3.
go back to reference Morris EJ, Maughan NJ, Forman D, Quirke P. Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology. Gut. 2007;56:1419–25.PubMedCrossRef Morris EJ, Maughan NJ, Forman D, Quirke P. Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology. Gut. 2007;56:1419–25.PubMedCrossRef
4.
go back to reference Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853–8.PubMedCrossRef Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853–8.PubMedCrossRef
5.
9.
go back to reference Schwind S, et al. Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: a cancer and leukemia Group B Study. J Clin Oncol. 2010;28:5257–64. Schwind S, et al. Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: a cancer and leukemia Group B Study. J Clin Oncol. 2010;28:5257–64.
10.
go back to reference Calin GA, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002;99:15524–9.PubMedCrossRef Calin GA, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002;99:15524–9.PubMedCrossRef
11.
go back to reference Cimmino A, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 2005;102:13944–9.PubMedCrossRef Cimmino A, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 2005;102:13944–9.PubMedCrossRef
12.
go back to reference Linsley PS, et al. Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol. 2007;27:2240–52.PubMedCrossRef Linsley PS, et al. Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol. 2007;27:2240–52.PubMedCrossRef
13.
go back to reference Chen RW, et al. Truncation in CCND1 mRNA alters miR-16–1 regulation in mantle cell lymphoma. Blood. 2008;112:822–9.PubMedCrossRef Chen RW, et al. Truncation in CCND1 mRNA alters miR-16–1 regulation in mantle cell lymphoma. Blood. 2008;112:822–9.PubMedCrossRef
14.
go back to reference Bonci D, et al. The miR-15a-miR-16–1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14:1271–7.PubMedCrossRef Bonci D, et al. The miR-15a-miR-16–1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14:1271–7.PubMedCrossRef
15.
16.
go back to reference Kulda V, et al. Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases. Cancer Genet Cytogenet. 2010;200:154–60. Kulda V, et al. Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases. Cancer Genet Cytogenet. 2010;200:154–60.
17.
go back to reference Schetter AJ, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–36.PubMedCrossRef Schetter AJ, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–36.PubMedCrossRef
18.
go back to reference Slaby O, et al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 2007;72:397–402.PubMedCrossRef Slaby O, et al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 2007;72:397–402.PubMedCrossRef
19.
go back to reference Wang S, et al. Improvement of tissue preparation for laser capture microdissection: application for cell type-specific miRNA expression profiling in colorectal tumors. BMC Genomics. 2010;11:163. Wang S, et al. Improvement of tissue preparation for laser capture microdissection: application for cell type-specific miRNA expression profiling in colorectal tumors. BMC Genomics. 2010;11:163.
20.
go back to reference Calin GA, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353:1793–801.PubMedCrossRef Calin GA, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353:1793–801.PubMedCrossRef
21.
go back to reference Nicoloso MS, et al. MicroRNAs–the micro steering wheel of tumour metastases. Nat Rev Cancer. 2009;9:293–302.PubMedCrossRef Nicoloso MS, et al. MicroRNAs–the micro steering wheel of tumour metastases. Nat Rev Cancer. 2009;9:293–302.PubMedCrossRef
22.
go back to reference Gaur A, et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007;67:2456–68.PubMedCrossRef Gaur A, et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007;67:2456–68.PubMedCrossRef
23.
go back to reference Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ. 2010;17:215–20. Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ. 2010;17:215–20.
24.
go back to reference Xu T, et al. MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology. 2009;50:113–21.PubMedCrossRef Xu T, et al. MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology. 2009;50:113–21.PubMedCrossRef
25.
go back to reference Flavin RJ, et al. Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma. Mod Pathol. 2009;22:197–205.PubMedCrossRef Flavin RJ, et al. Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma. Mod Pathol. 2009;22:197–205.PubMedCrossRef
26.
go back to reference Yang H, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008;68:425–33.PubMedCrossRef Yang H, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008;68:425–33.PubMedCrossRef
27.
go back to reference Lin SL, Chiang A, Chang D, Ying SY. Loss of mir-146a function in hormone-refractory prostate cancer. RNA. 2008;14:417–24.PubMedCrossRef Lin SL, Chiang A, Chang D, Ying SY. Loss of mir-146a function in hormone-refractory prostate cancer. RNA. 2008;14:417–24.PubMedCrossRef
28.
go back to reference Petillo D, et al. MicroRNA profiling of human kidney cancer subtypes. Int J Oncol. 2009;35:109–14.PubMedCrossRef Petillo D, et al. MicroRNA profiling of human kidney cancer subtypes. Int J Oncol. 2009;35:109–14.PubMedCrossRef
29.
go back to reference Wang YX, et al. Initial study of microRNA expression profiles of colonic cancer without lymph node metastasis. J Dig Dis. 2010;11:50–4. Wang YX, et al. Initial study of microRNA expression profiles of colonic cancer without lymph node metastasis. J Dig Dis. 2010;11:50–4.
30.
go back to reference Liu Q, et al. miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res. 2008;36:5391–404.PubMedCrossRef Liu Q, et al. miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res. 2008;36:5391–404.PubMedCrossRef
31.
go back to reference Xia H, et al. MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells. Biochem Biophys Res Commun. 2009;380:205–10.PubMedCrossRef Xia H, et al. MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells. Biochem Biophys Res Commun. 2009;380:205–10.PubMedCrossRef
32.
go back to reference Xia L, et al. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 2008;123:372–9.PubMedCrossRef Xia L, et al. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 2008;123:372–9.PubMedCrossRef
33.
go back to reference Staub E, et al. A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer. Mol Cancer. 2006;5:37. Staub E, et al. A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer. Mol Cancer. 2006;5:37.
34.
go back to reference Schumacher P, et al. The metastatic lymph node ratio predicts survival in colon cancer. Am J Surg. 2007;194:827–31 discussion 31–2. Schumacher P, et al. The metastatic lymph node ratio predicts survival in colon cancer. Am J Surg. 2007;194:827–31 discussion 31–2.
35.
go back to reference Mitchell PS, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–8.PubMedCrossRef Mitchell PS, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–8.PubMedCrossRef
Metadata
Title
Downregulation of miR-195 correlates with lymph node metastasis and poor prognosis in colorectal cancer
Authors
Xueqing Wang
Jiandong Wang
Henghui Ma
Jin Zhang
Xiaojun Zhou
Publication date
01-06-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9880-5

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