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Diagnostic Pathology
Published in: Diagnostic Pathology 1/2014

Open Access 01-12-2014 | Research

Decreased microRNA-224 and its clinical significance in non-small cell lung cancer patients

Authors: Dan Zhu, Hui Chen, Xiguang Yang, Weisong Chen, Linying Wang, Jilin Xu, Long Yu

Published in: Diagnostic Pathology | Issue 1/2014

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Abstract

Background

MicroRNA-224 has been proven dysregulated in some human malignancies and correlated with tumor progression. However, its expression and clinical significance in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to explore the effects of miR-224 in NSCLC tumorigenesis and development.

Methods

Using real-time quantitative RT-PCR, we detected miR-224 expression in NSCLC cell lines and primary tumor tissues. The association of miR-224 expression with clinicopathological factors and prognosis was also statistically analyzed. MTT, flow cytometric, Transwell invasion and migration assays, and scratch migration assay were used to test the proliferation, apoptosis, invasion, and migration of NSCLC cells after miR-224 mimics transfection.

Results

MiR-224 expression levels were significantly down-regulated in NSCLC compared to the corresponding noncancerous lung tissues (P <0.001). In addition, decreased miR-224 expression was significantly associated with lymph node metastasis (P = 0.002), advanced TNM stage (P <0.001), and shorter overall survival (P <0.001). Multivariate regression analysis corroborated that down-regulation of miR-224 was an independent unfavourable prognostic factor for patients with NSCLC. Furthermore, transfection of miR-224 mimics in NSCLC A549 cells was able to reduce cell proliferation, invasion, and migration, and promote cell apoptosis.

Conclusions

These findings indicate that miR-224 may act not only as a novel diagnostic and prognostic marker, but also as a potential target for miR-based therapy of NSCLC.

Virtual Slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​13000_​2014_​198
Appendix
Available only for authorised users
Literature
1.
Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin. 2010, 60: 277-300. 10.3322/caac.20073.PubMedCrossRef
2.
Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L, Kunkler I, Group E-W: Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data. Lancet Oncol. 2007, 8: 784-796. 10.1016/S1470-2045(07)70246-2.PubMedCrossRef
3.
Osman A: MicroRNAs in health and disease-basic science and clinical applications. Clin Lab. 2012, 58: 393-402.PubMed
4.
Zhao G, Cai C, Yang T, Qiu X, Liao B, Li W, Ji Z, Zhao J, Zhao H, Guo M, Ma Q, Xiao C, Fan Q, Ma B: MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS One. 2013, 8: e53906-10.1371/journal.pone.0053906.PubMedPubMedCentralCrossRef
5.
6.
Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5.PubMedCrossRef
7.
Dieckmann KP, Spiekermann M, Balks T, Flor I, Loning T, Bullerdiek J, Belge G: MicroRNAs miR-371-3 in serum as diagnostic tools in the management of testicular germ cell tumours. Br J Cancer. 2012, 107: 1754-1760. 10.1038/bjc.2012.469.PubMedPubMedCentralCrossRef
8.
Takahashi M, Cuatrecasas M, Balaguer F, Hur K, Toiyama Y, Castells A, Boland CR, Goel A: The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer. PLoS One. 2012, 7: e46684-10.1371/journal.pone.0046684.PubMedPubMedCentralCrossRef
9.
Liu X, Yu H, Cai H, Wang Y: The expression and clinical significance of miR-132 in gastric cancer patients. Diagn Pathol. 2014, 9: 57-10.1186/1746-1596-9-57.PubMedPubMedCentralCrossRef
10.
Meng W, Ye Z, Cui R, Perry J, Dedousi-Huebner V, Huebner A, Wang Y, Li B, Volinia S, Nakanishi H, Kim T, Suh SS, Ayers LW, Ross P, Croce CM, Chakravarti A, Jin VX, Lautenschlaeger T: MicroRNA-31 predicts the presence of lymph node metastases and survival in patients with lung adenocarcinoma. Clin Cancer Res. 2013, 19: 5423-5433. 10.1158/1078-0432.CCR-13-0320.PubMedCrossRef
11.
Liu XH, Lu KH, Wang KM, Sun M, Zhang EB, Yang JS, Yin DD, Liu ZL, Zhou J, Liu ZJ, De W, Wang ZX: MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5. BMC Cancer. 2012, 12: 348-10.1186/1471-2407-12-348.PubMedPubMedCentralCrossRef
12.
Li Y, Jiang Q, Xia N, Yang H, Hu C: Decreased expression of microRNA-375 in nonsmall cell lung cancer and its clinical significance. J Int Med Res. 2012, 40: 1662-1669. 10.1177/030006051204000505.PubMedCrossRef
13.
Wang XC, Wang W, Zhang ZB, Zhao J, Tan XG, Luo JC: Overexpression of miRNA-21 promotes radiation-resistance of non-small cell lung cancer. Radiat Oncol. 2013, 8: 146-10.1186/1748-717X-8-146.PubMedCrossRef
14.
Bian HB, Pan X, Yang JS, Wang ZX, De W: Upregulation of microRNA-451 increases cisplatin sensitivity of non-small cell lung cancer cell line (A549). J Exp Clin Cancer Res. 2011, 30: 20-10.1186/1756-9966-30-20.PubMedPubMedCentralCrossRef
15.
Scapoli L, Palmieri A, Lo Muzio L, Pezzetti F, Rubini C, Girardi A, Farinella F, Mazzotta M, Carinci F: MicroRNA expression profiling of oral carcinoma identifies new markers of tumor progression. Int J Immunopathol Pharmacol. 2010, 23: 1229-1234.PubMed
16.
Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Menard S, Croce CM: MicroRNA signatures in human ovarian cancer. Cancer Res. 2007, 67: 8699-8707. 10.1158/0008-5472.CAN-07-1936.PubMedCrossRef
17.
Goto Y, Nishikawa R, Kojima S, Chiyomaru T, Enokida H, Inoguchi S, Kinoshita T, Fuse M, Sakamoto S, Nakagawa M, Naya Y, Ichikawa T, Seki N: Tumour-suppressive microRNA-224 inhibits cancer cell migration and invasion via targeting oncogenic TPD52 in prostate cancer. FEBS Lett. 2014, 588: 1973-1982. 10.1016/j.febslet.2014.04.020.PubMedCrossRef
18.
Fellenberg J, Saehr H, Lehner B, Depeweg D: A microRNA signature differentiates between giant cell tumor derived neoplastic stromal cells and mesenchymal stem cells. Cancer Lett. 2012, 321: 162-168. 10.1016/j.canlet.2012.01.043.PubMedCrossRef
19.
Upraity S, Kazi S, Padul V, Shirsat NV: MiR-224 expression increases radiation sensitivity of glioblastoma cells. Biochem Biophys Res Commun. 2014, 448: 225-230. 10.1016/j.bbrc.2014.04.095.PubMedCrossRef
20.
Li Q, Ding C, Chen C, Zhang Z, Xiao H, Xie F, Lei L, Chen Y, Mao B, Jiang M, Li J, Wang D, Wang G: miR-224 promotion of cell migration and invasion by targeting Homeobox D 10 gene in human hepatocellular carcinoma. J Gastroenterol Hepatol. 2014, 29: 835-842. 10.1111/jgh.12429.PubMedCrossRef
21.
Boguslawska J, Wojcicka A, Piekielko-Witkowska A, Master A, Nauman A: MiR-224 targets the 3’UTR of type 1 5′-iodothyronine deiodinase possibly contributing to tissue hypothyroidism in renal cancer. PLoS One. 2011, 6: e24541-10.1371/journal.pone.0024541.PubMedPubMedCentralCrossRef
22.
Mees ST, Mardin WA, Sielker S, Willscher E, Senninger N, Schleicher C, Colombo-Benkmann M, Haier J: Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas. Ann Surg Oncol. 2009, 16: 2339-2350. 10.1245/s10434-009-0531-4.PubMedCrossRef
23.
Shen SN, Wang LF, Jia YF, Hao YQ, Zhang L, Wang H: Upregulation of microRNA-224 is associated with aggressive progression and poor prognosis in human cervical cancer. Diagn Pathol. 2013, 8: 69-10.1186/1746-1596-8-69.PubMedPubMedCentralCrossRef
24.
Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006, 9: 189-198. 10.1016/j.ccr.2006.01.025.PubMedCrossRef
25.
Lin ZY, Huang YQ, Zhang YQ, Han ZD, He HC, Ling XH, Fu X, Dai QS, Cai C, Chen JH, Liang YX, Jiang FN, Zhong WD, Wang F, Wu CL: MicroRNA-224 inhibits progression of human prostate cancer by downregulating TRIB1. Int J Cancer. 2014, 135: 541-550. 10.1002/ijc.28707.PubMedCrossRef
26.
Yuan K, Xie K, Fox J, Zeng H, Gao H, Huang C, Wu M: Decreased levels of miR-224 and the passenger strand of miR-221 increase MBD2, suppressing maspin and promoting colorectal tumor growth and metastasis in mice. Gastroenterology. 2013, 145: 853-864 e859. 10.1053/j.gastro.2013.06.008.PubMedPubMedCentralCrossRef
27.
Gokhale A, Kunder R, Goel A, Sarin R, Moiyadi A, Shenoy A, Mamidipally C, Noronha S, Kannan S, Shirsat NV: Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway. J Cancer Res Ther. 2010, 6: 521-529. 10.4103/0973-1482.77072.PubMedCrossRef
28.
Bryant JL, Britson J, Balko JM, Willian M, Timmons R, Frolov A, Black EP: A microRNA gene expression signature predicts response to erlotinib in epithelial cancer cell lines and targets EMT. Br J Cancer. 2012, 106: 148-156. 10.1038/bjc.2011.465.PubMedPubMedCentralCrossRef
29.
Wang Y, Ren J, Gao Y, Ma JZ, Toh HC, Chow P, Chung AY, Ooi LL, Lee CG: MicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival. PLoS One. 2013, 8: e68744-10.1371/journal.pone.0068744.PubMedPubMedCentralCrossRef
30.
Huang L, Dai T, Lin X, Zhao X, Chen X, Wang C, Li X, Shen H, Wang X: MicroRNA-224 targets RKIP to control cell invasion and expression of metastasis genes in human breast cancer cells. Biochem Biophys Res Commun. 2012, 425: 127-133. 10.1016/j.bbrc.2012.07.025.PubMedCrossRef
31.
Wotschofsky Z, Busch J, Jung M, Kempkensteffen C, Weikert S, Schaser KD, Melcher I, Kilic E, Miller K, Kristiansen G, Erbersdobler A, Jung K: Diagnostic and prognostic potential of differentially expressed miRNAs between metastatic and non-metastatic renal cell carcinoma at the time of nephrectomy. Clin Chim Acta. 2013, 416: 5-10. 10.1016/j.cca.2012.11.010.PubMedCrossRef
32.
Han Y, Chen J, Zhao X, Liang C, Wang Y, Sun L, Jiang Z, Zhang Z, Yang R, Chen J, Li Z, Tang A, Li X, Ye J, Guan Z, Gui Y, Cai Z: MicroRNA expression signatures of bladder cancer revealed by deep sequencing. PLoS One. 2011, 6: e18286-10.1371/journal.pone.0018286.PubMedPubMedCentralCrossRef
33.
Zhang GJ, Zhou H, Xiao HX, Li Y, Zhou T: Up-regulation of miR-224 promotes cancer cell proliferation and invasion and predicts relapse of colorectal cancer. Cancer Cell Int. 2013, 13: 104-10.1186/1475-2867-13-104.PubMedPubMedCentralCrossRef
34.
Zhu S, Sachdeva M, Wu F, Lu Z, Mo YY: Ubc9 promotes breast cell invasion and metastasis in a sumoylation-independent manner. Oncogene. 2010, 29: 1763-1772. 10.1038/onc.2009.459.PubMedPubMedCentralCrossRef
35.
Lichner Z, Mejia-Guerrero S, Ignacak M, Krizova A, Bao TT, Girgis AH, Youssef YM, Yousef GM: Pleiotropic action of renal cell carcinoma-dysregulated miRNAs on hypoxia-related signaling pathways. Am J Pathol. 2012, 180: 1675-1687. 10.1016/j.ajpath.2011.12.030.PubMedCrossRef
36.
Ke TW, Hsu HL, Wu YH, Chen WT, Cheng YW, Cheng CW: MicroRNA-224 suppresses colorectal cancer cell migration by targeting Cdc42. Dis Markers. 2014, 2014: 617150-10.1155/2014/617150.PubMedPubMedCentralCrossRef
37.
38.
Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N: Combinatorial microRNA target predictions. Nat Genet. 2005, 37: 495-500. 10.1038/ng1536.PubMedCrossRef
Metadata
Title
Decreased microRNA-224 and its clinical significance in non-small cell lung cancer patients
Authors
Dan Zhu
Hui Chen
Xiguang Yang
Weisong Chen
Linying Wang
Jilin Xu
Long Yu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2014
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-014-0198-4

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