Hostname: page-component-848d4c4894-x5gtn Total loading time: 0 Render date: 2024-06-03T11:55:56.092Z Has data issue: false hasContentIssue false

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

Published online by Cambridge University Press:  03 December 2013

Z Shen*
Affiliation:
Department of Otorhinolaryngology (Head and Neck Surgery), Lihuili Hospital of Ningbo University, Ningbo, China Institute of Biochemistry and Molecular Biology, Ningbo University School of Medicine, China
G Zhan
Affiliation:
Department of Otorhinolaryngology (Head and Neck Surgery), Yinzhou No.2 Hospital, Ningbo, China
H Deng
Affiliation:
Department of Otorhinolaryngology (Head and Neck Surgery), Lihuili Hospital of Ningbo University, Ningbo, China
Y Ren
Affiliation:
Department of Otorhinolaryngology (Head and Neck Surgery), Lihuili Hospital of Ningbo University, Ningbo, China
D Ye
Affiliation:
Department of Otorhinolaryngology (Head and Neck Surgery), Lihuili Hospital of Ningbo University, Ningbo, China
B Xiao
Affiliation:
Institute of Biochemistry and Molecular Biology, Ningbo University School of Medicine, China
J Guo
Affiliation:
Institute of Biochemistry and Molecular Biology, Ningbo University School of Medicine, China
*
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: szs7216@sina.com

Abstract

Objective:

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

Methods:

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.

Results:

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.

Conclusion:

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

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Jain, P, Kumar, P, Pai, VR, Parikh, PM. Neoadjuvant chemotherapy or chemoradiotherapy in head and neck cancer. Indian J Cancer 2008;45:83–9CrossRefGoogle ScholarPubMed
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:CR299304Google Scholar
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;10:306CrossRefGoogle ScholarPubMed
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;29:60CrossRefGoogle ScholarPubMed
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;88:709–17CrossRefGoogle ScholarPubMed
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;24:652–7CrossRefGoogle ScholarPubMed
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;9:1354–9CrossRefGoogle ScholarPubMed
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;84:6030–4CrossRefGoogle ScholarPubMed
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;345:312CrossRefGoogle ScholarPubMed
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;101:2987–92CrossRefGoogle ScholarPubMed
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;108:1657–65CrossRefGoogle ScholarPubMed
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;22:7146–54CrossRefGoogle Scholar
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;39:545–50CrossRefGoogle ScholarPubMed
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;124:1183–9CrossRefGoogle Scholar
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;400:97102CrossRefGoogle ScholarPubMed
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;45:1723CrossRefGoogle ScholarPubMed
17Bartel, DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281–97CrossRefGoogle ScholarPubMed
18Chekulaeva, M, Filipowicz, W. Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Curr Opin Cell Biol 2009;21:452–60CrossRefGoogle ScholarPubMed
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;33:220–5CrossRefGoogle ScholarPubMed
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;71:5659–69CrossRefGoogle ScholarPubMed
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;2:333–43CrossRefGoogle ScholarPubMed
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;105:20297–302CrossRefGoogle ScholarPubMed
23Khabar, KS. Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements. Cell Mol Life Sci 2010;67:2937–55CrossRefGoogle Scholar
24Abdelmohsen, K, Gorospe, M. Posttranscriptional regulation of cancer traits by HuR. Wiley Interdiscip Rev RNA 2010;1:214–29CrossRefGoogle ScholarPubMed
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;27:5365–80CrossRefGoogle Scholar
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;14:2738–47CrossRefGoogle ScholarPubMed
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;275:11750–7CrossRefGoogle ScholarPubMed
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):325–31CrossRefGoogle ScholarPubMed
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;27:283–96CrossRefGoogle ScholarPubMed
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;94:347–50CrossRefGoogle Scholar
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;11:7362–8CrossRefGoogle ScholarPubMed
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;128:360–8CrossRefGoogle ScholarPubMed
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;19:2340–50CrossRefGoogle ScholarPubMed
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;22:1804–15CrossRefGoogle ScholarPubMed
35Biggar, KK, Storey, KB. Perspectives in cell cycle regulation: lessons from an anoxic vertebrate. Curr Genomics 2009;10:573–84CrossRefGoogle ScholarPubMed