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MicroRNA-519a demonstrates significant tumour suppressive activity in laryngeal squamous cells by targeting anti-carcinoma HuR gene

  • Z Shen (a1) (a2), G Zhan (a3), H Deng (a1), Y Ren (a1), D Ye (a1), B Xiao (a2) and J Guo (a2)...



This study investigated the expression and functional effects, and related molecular mechanisms, of microRNA-519a in laryngeal squamous cell carcinoma.


MicroRNA-519a and HuR messenger RNA in laryngeal squamous cell carcinoma were measured using reverse transcription polymerase chain reaction. MicroRNA-519a effects on the growth of human epithelial type 2 cells were tested using an MTT assay. The influence of microRNA-519a on the expression levels of HuR and other related genes in protein was tested by Western blotting. Cell cycle analyses were performed using flow cytometry. Associations between expression levels and patients' clinical parameters were analysed with Pearson correlation analysis.


Expression of microRNA-519a in laryngeal squamous cell carcinoma tissues was significantly lower than in adjacent non-cancerous tissues. The expression of microRNA-519a was negatively associated with histological differentiation, tumour–node–metastasis stage, lymphatic metastasis and disease-free survival time. After increasing the level of microRNA-519a in laryngeal squamous cell carcinoma human epithelial type 2 cells, cell growth was inhibited and cell cycle was arrested in the G2/M phase. MicroRNA-519a down-regulated HuR gene expression in protein levels without affecting messenger RNA levels.


MicroRNA-519a may function as a tumour suppressor by inhibiting HuR expression, and may serve as a therapeutic target for laryngeal squamous cell carcinoma.


Corresponding author

Address for correspondence: Dr Z Shen, Department of Otorhinolaryngology (Head and Neck Surgery), Lihuili Hospital of Ningbo University, Ningbo 315040, China Fax: +86-574-87392232 E-mail:


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1Jain, P, Kumar, P, Pai, VR, Parikh, PM. Neoadjuvant chemotherapy or chemoradiotherapy in head and neck cancer. Indian J Cancer 2008;45:83–9
2Micozkadioğlu, D, Unal, M, Pata, YS, Baştürk, M, Cinel, L. Prognostic value of expression of p53, proliferating cell nuclear antigen, and c-erbB-2 in larynx squamous cell carcinoma. Med Sci Monit 2008;14:CR299304
3Che, XH, Chen, H, Xu, ZM, Shang, C, Sun, KL, Fu, WN. 14-3-3epsilon contributes to tumour suppression in larynx squamous cell carcinoma by affecting apoptosis and invasion. BMC Cancer 2010;10:306
4Wang, W, Lin, P, Han, C, Cai, W, Zhao, X, Sun, B. Vasculogenic mimicry contributes to lymph node metastasis of laryngeal squamous cell carcinoma. J Exp Clin Cancer Res 2010;29:60
5Zhou, H, Guo, JM, Lou, YR, Zhang, XJ, Zhong, FD, Jiang, Z et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. J Mol Med (Berl) 2010;88:709–17
6Guo, J, Miao, Y, Xiao, B, Huan, R, Jiang, Z, Meng, D et al. Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. J Gastroenterol Hepatol 2009;24:652–7
7Abdelmohsen, K, Kim, MM, Srikantan, S, Mercken, EM, Brennan, SE, Wilson, GM et al. MiR-519 suppresses tumor growth by reducing HuR levels. Cell Cycle 2010;9:1354–9
8Kruys, V, Wathelet, M, Poupart, P, Contreras, R, Fiers, W, Content, J et al. The 3' untranslated region of the human interferon-beta mRNA has an inhibitory effect on translation. Proc Natl Acad Sci U S A 1987;84:6030–4
9Hackermüller, J, Meisner, NC, Auer, M, Jaritz, M, Stadler, PF. The effect of RNA secondary structures on RNA-ligand binding and the modifier RNA mechanism: a quantitative model. Gene 2005;345:312
10López de Silanes, I, Zhan, M, Lal, A, Yang, X, Gorospe, M. Identification of a target RNA motif for RNA-binding protein HuR. Proc Natl Acad Sci U S A 2004;101:2987–92
11Dixon, DA, Tolley, ND, King, PH, Nabors, LB, McIntyre, TM, Zimmerman, GA et al. Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. J Clin Invest 2001;108:1657–65
12López de Silanes, I, Fan, J, Yang, X, Zonderman, AB, Potapova, O, Pizer, ES et al. Role of the RNA-binding protein HuR in colon carcinogenesis. Oncogene 2003;22:7146–54
13Cho, NP, Han, HS, Soh, Y, Lee, KY, Son, HJ. Cytoplasmic HuR over-expression is associated with increased cyclooxygenase-2 expression in laryngeal squamous cell carcinomas. Pathology 2007;39:545–50
14Shen, Z, Ye, D, Zhang, X, Jiang, Z, Xiao, B, Guo, J. Inhibitory effect of HuR gene small interfering RNA segment on larynx squamous cell carcinoma Hep-2 cell growth. J Laryngol Otol 2010;124:1183–9
15Xiao, B, Guo, J, Miao, Y, Jiang, Z, Huan, R, Zhang, Y et al. Detection of miR-106a in gastric carcinoma and its clinical significance. Clin Chim Acta 2009;400:97102
16Jiang, Z, Guo, J, Xiao, B, Miao, Y, Huang, R, Li, D et al. Increased expression of miR-421 in human gastric carcinoma and its clinical association. J Gastroenterol 2010;45:1723
17Bartel, DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281–97
18Chekulaeva, M, Filipowicz, W. Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Curr Opin Cell Biol 2009;21:452–60
19Nie, J, Liu, L, Zheng, W, Chen, L, Wu, X, Xu, Y et al. MicroRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2. Carcinogenesis 2012;33:220–5
20Ugras, S, Brill, E, Jacobsen, A, Hafner, M, Socci, ND, Decarolis, PL et al. Small RNA sequencing and functional characterization reveals MicroRNA-143 tumor suppressor activity in liposarcoma. Cancer Res 2011;71:5659–69
21Marasa, BS, Srikantan, S, Martindale, JL, Kim, MM, Lee, EK, Gorospe, M et al. MicroRNA profiling in human diploid fibroblasts uncovers miR-519 role in replicative senescence. Aging (Albany NY) 2010;2:333–43
22Abdelmohsen, K, Srikantan, S, Kuwano, Y, Gorospe, M. miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels. Proc Natl Acad Sci U S A 2008;105:20297–302
23Khabar, KS. Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements. Cell Mol Life Sci 2010;67:2937–55
24Abdelmohsen, K, Gorospe, M. Posttranscriptional regulation of cancer traits by HuR. Wiley Interdiscip Rev RNA 2010;1:214–29
25Dormoy-Raclet, V, Ménard, I, Clair, E, Kurban, G, Mazroui, R, Di Marco, S et al. The RNA-binding protein HuR promotes cell migration and cell invasion by stabilizing the beta-actin mRNA in a U-rich-element-dependent manner. Mol Cell Biol 2007;27:5365–80
26Kolev, Y, Uetake, H, Iida, S, Ishikawa, T, Kawano, T, Sugihara, K. Prognostic significance of VEGF expression in correlation with COX-2, microvessel density, and clinicopathological characteristics in human gastric carcinoma. Ann Surg Oncol 2007;14:2738–47
27Dixon, DA, Kaplan, CD, McIntyre, TM, Zimmerman, GA, Prescott, SM. Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 3'-untranslated region. J Biol Chem 2000;275:11750–7
28Ristimäki, A, Narko, K, Hla, T. Down-regulation of cytokine-induced cyclo-oxygenase-2 transcript isoforms by dexamethasone: evidence for post-transcriptional regulation. Biochem J 1996;318(pt 1):325–31
29Tong, X, Van Dross, RT, Abu-Yousif, A, Morrison, AR, Pelling, JC. Apigenin prevents UVB-induced cyclooxygenase 2 expression: coupled mRNA stabilization and translational inhibition. Mol Cell Biol 2007;27:283–96
30Do, SI, Araujo, ES, Kalil, RK, Bacchini, P, Bertoni, F, Unni, KK et al. Expression of embryonic lethal abnormal vision (ELAV)-like protein HuR and cyclooxygenase-2 (COX-2) in Ewing sarcoma. Tumori 2008;94:347–50
31Mrena, J, Wiksten, JP, Thiel, A, Kokkola, A, Pohjola, L, Lundin, J et al. Cyclooxygenase-2 is an independent prognostic factor in gastric cancer and its expression is regulated by the messenger RNA stability factor HuR. Clin Cancer Res 2005;11:7362–8
32Park, GB, Song, H, Kim, YS, Sung, M, Ryu, JW, Lee, HK et al. Cell cycle arrest induced by engagement of B7-H4 on Epstein-Barr virus-positive B-cell lymphoma cell lines. Immunology 2009;128:360–8
33Wang, W, Caldwell, MC, Lin, S, Furneaux, H, Gorospe, M. HuR regulates cyclin A and cyclin B1 mRNA stability during cell proliferation. EMBO J 2000;19:2340–50
34Kim, HH, Abdelmohsen, K, Lal, A, Pullmann, R Jr, Yang, X, Galban, S et al. Nuclear HuR accumulation through phosphorylation by Cdk1. Genes Dev 2008;22:1804–15
35Biggar, KK, Storey, KB. Perspectives in cell cycle regulation: lessons from an anoxic vertebrate. Curr Genomics 2009;10:573–84


MicroRNA-519a demonstrates significant tumour suppressive activity in laryngeal squamous cells by targeting anti-carcinoma HuR gene

  • Z Shen (a1) (a2), G Zhan (a3), H Deng (a1), Y Ren (a1), D Ye (a1), B Xiao (a2) and J Guo (a2)...


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