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

Diagnostic Pathology

Hui Wang²  Lin Zhang²  Yu-qing Hao¹  Yong-feng Jia⁴  Ling-feng Wang³  Shu-na Shen² 

[1] Dermatological Department, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou 014010, China;Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou 014010, China;Department of Burn, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou 014010, China;Pathology Department, The First Affiliated Hospital of Inner Mongolia Medical University, Huhehot 010050, China

关键词: Prognosis;    Real-time quantitative RT-PCR assay;    Cervical cancer;    MicroRNA-224;   

Others  :  807114
DOI  :  10.1186/1746-1596-8-69

 received in 2013-03-25, accepted in 2013-04-19,  发布年份 2013

【 摘 要 】

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.diagnosticpathology.diagnomx.eu/vs/2170449349527493 webcite

【 授权许可】

   
2013 Shen et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 2012, 62:10-29.
• [2]Waggoner SE: Cervical cancer. Lancet 2003, 361:2217-2225.
• [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.
• [4]Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116:281-297.
• [5]Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell 2009, 136:215-233.
• [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.
• [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.
• [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. BioMed Central Full Text
• [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]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.
• [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.
• [12]Lajer CB, Garn?s 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.
• [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.
• [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.
• [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.
• [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.
• [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. BioMed Central Full Text
• [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. BioMed Central Full Text
• [20]Pereira PM, Marques JP, Soares AR, Carreto L, Santos MA: MicroRNA expression variability in human cervical tissues. PLoS One 2010, 5:e11780.
• [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.
• [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. BioMed Central Full Text
• [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. BioMed Central Full Text
• [24]Hu X, Schwarz JK, Lewis JS Jr, Huettner PC, Rader JS, Deasy JO, Grigsby PW, Wang X: A microRNA expression signature for cervical cancer prognosis. Cancer Res 2010, 70:1441-1448.
• [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. BioMed Central Full Text
• [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. BioMed Central Full Text
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [36]Donadeu FX, Schauer SN, Sontakke SD: Involvement of miRNAs in ovarian follicular and luteal development. J Endocrinol 2012, 215:323-34.
• [37]Mavridis K, Stravodimos K, Scorilas A: Downregulation and Prognostic Performance of MicroRNA 224 Expression in Prostate Cancer. Clin Chem 2013, 59:261-269.
• [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.