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Published in: Diagnostic Pathology 1/2015

Open Access 01-12-2015 | Research

Decreased expression of microRNA-124 is an independent unfavorable prognostic factor for patients with breast cancer

Authors: Liang-liang Dong, Li-ming Chen, Wei-min Wang, Liang-ming Zhang

Published in: Diagnostic Pathology | Issue 1/2015

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Abstract

Background

MicroRNA-124 (miR-124) has been reported to be downregulated in breast cancer. However, its clinical significance and prognostic value in breast cancer have not been extensively studied.

Methods

The tissue expression levels of miR-124 were measured using quantitative real-time PCR in 133 breast cancer patients. The correlation between the miR-124 levels and the clinicopathological factors of the patients was also analyzed. Survival and Cox proportional-hazards regression analyses were performed to determine the correlation between miR-124 expression levels and prognosis in the patients.

Results

Quantitative real-time PCR analysis showed that miR-124 had lower expression in breast cancer specimens than that in matched adjacent normal breast tissues (0.39 ± 0.16 vs. 1.00 ± 0.39; P < 0.05). Low miR-124 expression level was significantly associated with advanced TNM stage (P = 0.011), lymph node metastasis (P = 0.012), and poorer pathological differentiation (P = 0.023). A significant difference was found that breast cancer patients with low miR-124 expression level had distinctly shorter overall survival than patients with high miR-124 expression level (63.8% vs. 35.2%, P = 0.03). Furthermore, multivariate analysis of the prognosis factors with a Cox proportional hazards model confirmed that low miR-124 expression was a significant independent predictor of poor survival in breast cancer (HR = 3.16, 95% CI: 1.79-9.13, P = 0.017).

Conclusion

These findings proved that the decreased expression of miR-124 might be associated with tumor progression and poor prognosis in patients with breast cancer.

Virtual Slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​3752603721493544​
Literature
1.
go back to reference Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212–36.CrossRefPubMed Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212–36.CrossRefPubMed
4.
go back to reference Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. Jama. 2008;299(4):425–36.CrossRefPubMedCentralPubMed Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. Jama. 2008;299(4):425–36.CrossRefPubMedCentralPubMed
5.
go back to reference Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 2008;13(1):48–57.CrossRefPubMed Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 2008;13(1):48–57.CrossRefPubMed
6.
go back to reference Fulci V, Chiaretti S, Goldoni M, Azzalin G, Carucci N, Tavolaro S, et al. Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood. 2007;109(11):4944–51.CrossRefPubMed Fulci V, Chiaretti S, Goldoni M, Azzalin G, Carucci N, Tavolaro S, et al. Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood. 2007;109(11):4944–51.CrossRefPubMed
7.
go back to reference Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.CrossRefPubMed Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.CrossRefPubMed
8.
go back to reference Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005;334(4):1351–8.CrossRefPubMed Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005;334(4):1351–8.CrossRefPubMed
9.
go back to reference Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ, et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol. 2007;8(10):R214.CrossRefPubMedCentralPubMed Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ, et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol. 2007;8(10):R214.CrossRefPubMedCentralPubMed
10.
go back to reference Lee MR, Kim JS. Kim KS: miR-124a is important for migratory cell fate transition during gastrulation of human embryonic stem cells. Stem Cells. 2010;28(9):1550–9.CrossRefPubMed Lee MR, Kim JS. Kim KS: miR-124a is important for migratory cell fate transition during gastrulation of human embryonic stem cells. Stem Cells. 2010;28(9):1550–9.CrossRefPubMed
11.
go back to reference Cheng LC, Pastrana E, Tavazoie M, Doetsch F. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci. 2009;12(4):399–408.CrossRefPubMedCentralPubMed Cheng LC, Pastrana E, Tavazoie M, Doetsch F. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci. 2009;12(4):399–408.CrossRefPubMedCentralPubMed
12.
go back to reference Han ZB, Yang Z, Chi Y, Zhang L, Wang Y, Ji Y, et al. MicroRNA-124 suppresses breast cancer cell growth and motility by targeting CD151. Cell Physiol Biochem. 2013;31(6):823–32.CrossRefPubMed Han ZB, Yang Z, Chi Y, Zhang L, Wang Y, Ji Y, et al. MicroRNA-124 suppresses breast cancer cell growth and motility by targeting CD151. Cell Physiol Biochem. 2013;31(6):823–32.CrossRefPubMed
13.
go back to reference Wang P, Chen L, Zhang J, Chen H, Fan J, Wang K, et al. Methylation-mediated silencing of the miR-124 genes facilitates pancreatic cancer progression and metastasis by targeting Rac1. Oncogene. 2014;33(4):514–24.CrossRefPubMed Wang P, Chen L, Zhang J, Chen H, Fan J, Wang K, et al. Methylation-mediated silencing of the miR-124 genes facilitates pancreatic cancer progression and metastasis by targeting Rac1. Oncogene. 2014;33(4):514–24.CrossRefPubMed
14.
go back to reference Shi XB, Xue L, Ma AH, Tepper CG, Gandour-Edwards R, Kung HJ, et al. Tumor suppressive miR-124 targets androgen receptor and inhibits proliferation of prostate cancer cells. Oncogene. 2013;32(35):4130–8.CrossRefPubMedCentralPubMed Shi XB, Xue L, Ma AH, Tepper CG, Gandour-Edwards R, Kung HJ, et al. Tumor suppressive miR-124 targets androgen receptor and inhibits proliferation of prostate cancer cells. Oncogene. 2013;32(35):4130–8.CrossRefPubMedCentralPubMed
15.
go back to reference Xia J, Wu Z, Yu C, He W, Zheng H, He Y, et al. miR-124 inhibits cell proliferation in gastric cancer through down-regulation of SPHK1. J Pathol. 2012;227(4):470–80.CrossRefPubMed Xia J, Wu Z, Yu C, He W, Zheng H, He Y, et al. miR-124 inhibits cell proliferation in gastric cancer through down-regulation of SPHK1. J Pathol. 2012;227(4):470–80.CrossRefPubMed
16.
go back to reference Zheng F, Liao YJ, Cai MY, Liu YH, Liu TH, Chen SP, et al. The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2. Gut. 2012;61(2):278–89.CrossRefPubMed Zheng F, Liao YJ, Cai MY, Liu YH, Liu TH, Chen SP, et al. The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2. Gut. 2012;61(2):278–89.CrossRefPubMed
17.
go back to reference Li L, Luo J, Wang B, Wang D, Xie X, Yuan L, et al. Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer. Mol Cancer. 2013;12:163.CrossRefPubMedCentralPubMed Li L, Luo J, Wang B, Wang D, Xie X, Yuan L, et al. Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer. Mol Cancer. 2013;12:163.CrossRefPubMedCentralPubMed
18.
go back to reference Profumo V, Gandellini P. MicroRNAs: cobblestones on the road to cancer metastasis. Crit Rev Oncog. 2013;18(4):341–55.CrossRefPubMed Profumo V, Gandellini P. MicroRNAs: cobblestones on the road to cancer metastasis. Crit Rev Oncog. 2013;18(4):341–55.CrossRefPubMed
20.
go back to reference Carleton M, Cleary MA, Linsley PS. MicroRNAs and cell cycle regulation. Cell Cycle. 2007;6(17):2127–32.CrossRefPubMed Carleton M, Cleary MA, Linsley PS. MicroRNAs and cell cycle regulation. Cell Cycle. 2007;6(17):2127–32.CrossRefPubMed
22.
go back to reference Svoboda M, Sana J, Redova M, Navratil J, Palacova M, Fabian P, et al. MiR-34b is associated with clinical outcome in triple-negative breast cancer patients. Diagn Pathol. 2012;7:31.CrossRefPubMedCentralPubMed Svoboda M, Sana J, Redova M, Navratil J, Palacova M, Fabian P, et al. MiR-34b is associated with clinical outcome in triple-negative breast cancer patients. Diagn Pathol. 2012;7:31.CrossRefPubMedCentralPubMed
23.
go back to reference Li W, Zang W, Liu P, Wang Y, Du Y, Chen X, et al. MicroRNA-124 inhibits cellular proliferation and invasion by targeting Ets-1 in breast cancer. Tumour Biol. 2014;35(11):10897–904.CrossRefPubMed Li W, Zang W, Liu P, Wang Y, Du Y, Chen X, et al. MicroRNA-124 inhibits cellular proliferation and invasion by targeting Ets-1 in breast cancer. Tumour Biol. 2014;35(11):10897–904.CrossRefPubMed
Metadata
Title
Decreased expression of microRNA-124 is an independent unfavorable prognostic factor for patients with breast cancer
Authors
Liang-liang Dong
Li-ming Chen
Wei-min Wang
Liang-ming Zhang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2015
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-015-0257-5

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