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Diagnostic Pathology
Published in: Diagnostic Pathology 1/2013

Open Access 01-12-2013 | Research

Upregulation of microRNA-224 is associated with aggressive progression and poor prognosis in human cervical cancer

Authors: Shu-na Shen, Ling-feng Wang, Yong-feng Jia, Yu-qing Hao, Lin Zhang, Hui Wang

Published in: Diagnostic Pathology | Issue 1/2013

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Abstract

Objective

Accumulating evidence for differential expression of microRNA-224 (miR-224) in various types of human cancer suggests that it may be play a crucial role in tumor biology. The previous microarray detection also shown that miR-224 was one of miRNAs with significant upregulation in cervical cancer tissues relative to adjacent normal tissues. However, little is known about the function of miR-224 in human cervical cancer. The aim of this study was to investigate the clinical significance of miR-224 expression in cervical cancer.

Methods

MiR-224 expression in 126 pairs of fresh human cervical cancer and adjacent normal tissues was measured by real-time quantitative RT-PCR assay.

Results

miR-224 expression was significantly upregulated in cervical cancer tissues when compared with corresponding adjacent normal tissues (P < 0.001). It was also significantly higher in the cancerous tissues of patients with advanced FIGO stage cervical cancer than those with early FIGO stage (P = 0.02). In addition, miR-224 was expressed at significantly higher levels in lymph node metastasis-positive patients than in lymph node metastasis-negative patients (P = 0.008). Moreover, we found that lesser differentiated tumors expressed higher miR-224 (P = 0.03). Finally, there were sufficient evidence to confirm its value in the status of vascular invasion (P = 0.01) and human papillomavirus (HPV) infection (P = 0.02) in cervical cancer. More importantly, Kaplan-Meier analysis showed that cervical cancer patients with high miR-224 expression tend to have shorter overall survival. In multivariate analysis stratified for known prognostic variables, miR-224 was identified as an independent prognostic marker.

Conclusion

Our data indicated that miR-224 upregulation was associated with aggressive progression and poor prognosis in cervical cancer. MiR-224 was identified for the first time as an independent marker for predicting the clinical outcome of cervical cancer patients.

Virtual slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​2170449349527493​
Appendix
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Literature
1.
Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 2012, 62: 10-29. 10.3322/caac.20138.CrossRefPubMed
2.
3.
Forouzanfar MH F, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ, Naghavi M: Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet. 2011, 378: 1461-1484. 10.1016/S0140-6736(11)61351-2.CrossRefPubMed
4.
Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5.CrossRefPubMed
5.
6.
Guo H, Ingolia NT, Jonathan S, Weissman JS, Bartel DP: Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010, 466: 835-840. 10.1038/nature09267.PubMedCentralCrossRefPubMed
7.
Chen PJ, Yeh SH, Liu WH, Lin CC, Huang HC, Chen CL, Chen DS, Chen PJ: Androgen pathway stimulates microRNA-216a transcription to suppress the tumor suppressor in lung cancer-1 gene in early hepatocarcinogenesis. Hepatology. 2012, 56: 632-643.CrossRefPubMed
8.
Fu J, Tang W, Du P, Wang G, Chen W, Li J, Zhu Y, Gao J, Cui L: Identifying microRNA-mRNA regulatory network in colorectal cancer by a combination of expression profile and bioinformatics analysis. BMC Syst Biol. 2012, 6: 68-10.1186/1752-0509-6-68.PubMedCentralCrossRefPubMed
9.
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.CrossRefPubMed
10.
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.CrossRefPubMed
11.
Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, Zheng ZM: Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One. 2008, 3: e2557-10.1371/journal.pone.0002557.PubMedCentralCrossRefPubMed
12.
Lajer CB, Garnæs E, Friis-Hansen L, Norrild B, Therkildsen MH, Glud M, Rossing M, Lajer H, Svane D, Skotte L, Specht L, Buchwald C, Nielsen FC: The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging between HPV-related head and neck cancer and cervical cancer. Br J Cancer. 2012, 106: 1526-1534. 10.1038/bjc.2012.109.PubMedCentralCrossRefPubMed
13.
Xu J, Li Y, Wang F, Wang X, Cheng B, Ye F, Xie X, Zhou C, Lu W: Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer. Oncogene. 2013, 32: 976-987. 10.1038/onc.2012.121.CrossRefPubMed
14.
Liu L, Yu X, Guo X, Tian Z, Su M, Long Y, Huang C, Zhou F, Liu M, Wu X, Wang X: miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2. Mol Med Report. 2012, 5: 753-760.
15.
Xie H, Zhao Y, Caramuta S, Larsson C, Lui WO: miR-205 Expression Promotes Cell Proliferation and Migration of Human Cervical Cancer Cells. PLoS One. 2012, 7: e46990-10.1371/journal.pone.0046990.PubMedCentralCrossRefPubMed
16.
Rao Q, Shen Q, Zhou H, Peng Y, Li J, Lin Z: Aberrant microRNA expression in human cervical carcinomas. Med Oncol. 2012, 29: 1242-1248. 10.1007/s12032-011-9830-2.CrossRefPubMed
17.
Au Yeung CL, Tsang TY, Yau PL, Kwok TT: Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway. Oncogene. 2011, 30: 2401-2410. 10.1038/onc.2010.613.CrossRefPubMed
18.
Chen S, Yang Z, Zhang Y, Qiao Y, Cui B, Zhang Y, Kong B: Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia. Diagn Pathol. 2012, 7: 40-10.1186/1746-1596-7-40.PubMedCentralCrossRefPubMed
19.
Han H, Yang Y, Lu Z, He Q, Lin Z: Decreased D2-40 and increased p16INK4A immunoreactivities correlate with higher grade of cervical intraepithelial neoplasia. Diagn Pathol. 2011, 6: 59-10.1186/1746-1596-6-59.PubMedCentralCrossRefPubMed
20.
Pereira PM, Marques JP, Soares AR, Carreto L, Santos MA: MicroRNA expression variability in human cervical tissues. PLoS One. 2010, 5: e11780-10.1371/journal.pone.0011780.PubMedCentralCrossRefPubMed
21.
Li JH, Xiao X, Zhang YN, Wang YM, Feng LM, Wu YM, Zhang YX: MicroRNA miR-886-5p inhibits apoptosis by down-regulating Bax expression in human cervical carcinoma cells. Gynecol Oncol. 2011, 120: 145-151. 10.1016/j.ygyno.2010.09.009.CrossRefPubMed
22.
Gong L, Zhang WD, Liu XY, Han XJ, Yao L, Zhu SJ, Lan M, Li YH, Zhang W: Clonal status and clinicopathological observation of cervical minimal deviation adenocarcinoma. Diagn Pathol. 2010, 5: 25-10.1186/1746-1596-5-25.PubMedCentralCrossRefPubMed
23.
García-Espinosa B, Nieto-Bona MP, Rueda S, Silva-Sánchez LF, Piernas-Morales MC, Carro-Campos P, Cortés-Lambea L, Moro-Rodríguez E: Genotype distribution of cervical human papillomavirus DNA in women with cervical lesions in Bioko. Equatorial Guinea. Diagn Pathol. 2009, 4: 31-10.1186/1746-1596-4-31.PubMedCentralCrossRefPubMed
24.
Hu X, Schwarz JK, Lewis JS, Huettner PC, Rader JS, Deasy JO, Grigsby PW, Wang X: A microRNA expression signature for cervical cancer prognosis. Cancer Res. 2010, 70: 1441-1448. 10.1158/0008-5472.CAN-09-3289.PubMedCentralCrossRefPubMed
25.
Liu H, Liu S, Wang H, Xie X, Chen X, Zhang X, Zhang Y: Genomic amplification of the human telomerase gene (hTERC) associated with human papillomavirus is related to the progression of uterine cervical dysplasia to invasive cancer. Diagn Pathol. 2012, 7: 147-10.1186/1746-1596-7-147.PubMedCentralCrossRefPubMed
26.
Imura J, Uchida Y, Nomoto K, Ichikawa K, Tomita S, Iijima T, Fujimori T: Laminin-5 is a biomarker of invasiveness in cervical adenocarcinoma. Diagn Pathol. 2012, 7: 105-10.1186/1746-1596-7-105.PubMedCentralCrossRefPubMed
27.
Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foa R, Schliwka J, Fuchs U, Novosel A, Muller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M: A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007, 129: 1401-1414. 10.1016/j.cell.2007.04.040.PubMedCentralCrossRefPubMed
28.
Wang Y, Toh HC, Chow P, Chung AY, Meyers DJ, Cole PA, Ooi LL, Lee CG: MicroRNA-224 is up-regulated in hepatocellular carcinoma through epigenetic mechanisms. FASEB J. 2012, 26: 3032-3041. 10.1096/fj.11-201855.PubMedCentralCrossRefPubMed
29.
Zhang Y, Takahashi S, Tasaka A, Yoshima T, Ochi H, Chayama K: Involvement of microRNA-224 in cell proliferation, migration, invasion and anti-apoptosis in hepatocellular carcinoma. J Gastroenterol Hepatol. 2013, 28: 565-575. 10.1111/j.1440-1746.2012.07271.x.CrossRefPubMed
30.
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: 521-9. 10.4103/0973-1482.77072.CrossRefPubMed
31.
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.CrossRefPubMed
32.
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.CrossRefPubMed
33.
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.CrossRefPubMed
34.
Mian C, Pennelli G, Fassan M, Balistreri M, Barollo S, Cavedon E, Galuppini F, Pizzi M, Vianello F, Pelizzo MR, Girelli ME, Rugge M, Opocher G: MicroRNA profiles in familial and sporadic medullary thyroid carcinoma: preliminary relationships with RET status and outcome. Thyroid. 2012, 22: 890-896. 10.1089/thy.2012.0045.PubMedCentralCrossRefPubMed
35.
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.PubMedCentralCrossRefPubMed
36.
Donadeu FX, Schauer SN, Sontakke SD: Involvement of miRNAs in ovarian follicular and luteal development. J Endocrinol. 2012, 215: 323-34. 10.1530/JOE-12-0252.CrossRefPubMed
37.
Mavridis K, Stravodimos K, Scorilas A: Downregulation and Prognostic Performance of MicroRNA 224 Expression in Prostate Cancer. Clin Chem. 2013, 59: 261-269. 10.1373/clinchem.2012.191502.CrossRefPubMed
38.
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
Metadata
Title
Upregulation of microRNA-224 is associated with aggressive progression and poor prognosis in human cervical cancer
Authors
Shu-na Shen
Ling-feng Wang
Yong-feng Jia
Yu-qing Hao
Lin Zhang
Hui Wang
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2013
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-8-69

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