Background Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer whose underlying molecular mechanisms are poorly understood. The natural antisense transcript (NAT) WRAP53 regulates p53 expression and WRAP53 protein is a component of telomerase. NATs play key roles in carcinogenesis, and although WRAP53 is known to increase cancer cell survival, its role in ESCC clinicopathology is unknown. The aim of this study was to investigate WRAP53 expression in ESCC and to correlate it with clinicopathological characteristics. Methods WRAP53 mRNA and protein expression was measured by quantitative PCR (qRT-PCR) and western blotting, respectively, in 4 ESSC cells lines and in 45 paired ESCC and non-neoplastic esophageal mucosa tissues. To correlate WRAP53 protein expression with clinicopathological characteristics, immunohistochemistry (IHC) was performed on 134 ESCC and 85 non-neoplastic esophageal mucosa tissues. Results Expression of WRAP53 was detected in all ESCC cell lines and was upregulated in the ESCC tissues compared with the corresponding non-neoplastic tissues (P<0.01). More cells expressed WRAP53 protein in the ESCC tissues than in the non-neoplastic tissues (P<0.01). Overexpression of WRAP53 was significantly correlated with tumor infiltration depth (P = 0.000), clinical stage (P = 0.001), and lymph node metastasis (P = 0.025). Wrap53 expression was not correlated with age, gender, or tumor differentiation. Conclusion This report indicates increased expression of WRAP53 in ESCC and that WRAP53 overexpression is correlated with tumor progression. WRAP53 may play a significant role in ESCC; accordingly, WRAP53 could be a useful biomarker for ESCC.
References
[1]
Faghihi MA, Wahlestedt C (2009) Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol 10: 637–643. doi: 10.1038/nrm2738
[2]
Lin M, Wu J, Shan G (2012) Noncoding RNAs: Different roles in tumorigenesis. Molecular Biology 57: 959–965. doi: 10.1007/s11434-011-4917-x
[3]
Berteaux N, Aptel N, Cathala G, Genton C, Coll J, et al. (2008) A Novel H19 Antisense RNA Overexpressed in Breast Cancer Contributes to Paternal IGF2 Expression. Molecular and Cellular Biology 28: 6731–6745. doi: 10.1128/mcb.02103-07
[4]
Rossignol F, Vaché C, Clottes E (2002) Natural antisense transcripts of hypoxia inducible factor 1 alpha are detected in different normal and tumour human tissues. Gene 299: 135–140. doi: 10.1016/s0378-1119(02)01049-1
[5]
Oto OA, Paydas S, Tanriverdi K, Seydaoglu G, Yavuz S, et al. (2007) Survivin and EPR-1 expression in acute leukemias: prognostic significance and review of the literature. Leuk Res 31: 1495–1501. doi: 10.1016/j.leukres.2007.01.005
[6]
Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, et al. (2008) Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451: 202–206. doi: 10.1038/nature06468
[7]
Yao XQ, Liu FK, Li JS, Qi XP, Wu B, et al. (2004) Significance of effector protease receptor-1 expression and its relationship with proliferation and apoptotic index in patients with primary advanced gastric adenocarcinoma. . World J Gastroenterol. 10: 1262–1267.
[8]
Zhang SC, Barclay C, Alexander LA, Geldenhuys L, Porter GA, et al.. (2007) Alternative splicing of the FGF antisense gene: differential subcellular localization in human tissues and esophageal adenocarcinoma. J Mol Med (Berl) 85:1215 –1228.
[9]
Dolnick BJ, Angelino NJ, Dolnick R, Sufrin JR (2003) A novel function for the rTS gene. Cancer Biol Ther 2: 364–369. doi: 10.4161/cbt.2.4.424
[10]
Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, et al. (2002) The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat 19: 607–614. doi: 10.1002/humu.10081
[11]
Zuckerman V, Wolyniec K, Sionov RV, Haupt S, Haupt Y (2009) Tumour suppression by p53: the importance of apoptosis and cellular senescence. J Pathol 219: 3–15. doi: 10.1002/path.2584
[12]
Farnebo M, Bykov VJ, Wiman KG (2010) The p53 tumor suppressor: a master regulator of diverse cellular processes and therapeutic target in cancer. Biochem Biophys Res Commun 396: 85–89. doi: 10.1016/j.bbrc.2010.02.152
[13]
Mahmoudi S, Henriksson S, Corcoran M, Méndez-Vidal C, Wiman KG, et al. (2001) Wrap53, a Natural p53 Antisense Transcript Required for p53 Induction upon DNA Damage. Molecular Cell 33: 462–471. doi: 10.1016/j.molcel.2009.01.028
[14]
Mahmoudi S, Henriksson S, Weibrecht I, Smith S, S？derberg O, et al. (2010) WRAP53 Is Essential for Cajal Body Formation and for Targeting the Survival of Motor Neuron Complex to Cajal Bodies. PLoS Biol 8: e1000521. doi: 10.1371/journal.pbio.1000521
[15]
Venteicher AS, Artandi SE (2009) TCAB1 Driving telomerase to Cajal bodies. Cell Cycle 8: 1329–1331. doi: 10.4161/cc.8.9.8288
[16]
Xu XC (2009) Risk factors and gene expression in esophageal cancer. Methods Mol Biol 471: 335–360. doi: 10.1007/978-1-59745-416-2_17
[17]
Wang N, Dong XJ, Zhou RM, Guo W, Zhang XJ, et al. (2009) An investigation on the polymorphisms of two DNA repair genes and susceptibility to ESCC and GCA of high-incidence region in northern China. Mol Biol Rep 36: 357–364. doi: 10.1007/s11033-007-9187-y
[18]
Lin DC, Du XL, Wang MR (2009) Protein alterations in ESCC and clinical implications: a review. Dis Esophagus 22: 9–20. doi: 10.1111/j.1442-2050.2008.00845.x
[19]
Lam AK (2000) Molecular biology of esophageal squamous cell carcinoma. Crit Rev Oncol Hematol 33: 71–90. doi: 10.1016/s1040-8428(99)00054-2
[20]
Dong Wang L, Bin Yue W, Zhou Y, Wei Feng C, Liu B, et al. (2002) Endoscopic screening and determination of p53 and proliferating cell nuclear antigen in esophageal multistage carcinogenes is: a comparative study between high and low risk populations in Henan, northern China. Dis Esophagus 15: 80–84. doi: 10.1046/j.1442-2050.2002.00228.x
[21]
Farnebo M (2009) Wrap53, a novel regulator of p53. Cell Cycle 8: 2343–2346. doi: 10.4161/cc.8.15.9223
[22]
Lu XF, Li EM, Du ZP, Xie JJ, Guo ZY, et al. (2010) Specificity protein 1 regulates fascin expression in esophageal squamous cell carcinoma as the result of the epidermal growth factor/extracellular signal-regulated kinase signaling pathway activation. Cell Mol Life Sci 67: 3313–3329. doi: 10.1007/s00018-010-0382-y
[23]
Shimada Y, Imamura M, Wagata T, Yamaguchi N, Tobe T (1992) Characterization of 21 newly established esophageal cancer cell lines. Cancer 69: 277–284. doi: 10.1002/1097-0142(19920115)69:2<277::aid-cncr2820690202>3.0.co;2-c
[24]
Liang B, Song X, Liu G, Li R, Xie J, et al. (2007) Involvement of TR3/Nur77 translocation to the endoplasmic reticulum in ER stress-induced apoptosis. Exp Cell Res 313: 2833–2844. doi: 10.1016/j.yexcr.2007.04.032
[25]
Rice TW, Blackstone EH, Rusch VW (2010) 7th edition of the AJCC Cancer Staging Manual: esophagus and esophagogastric junction. Ann Surg Oncol 17: 1721–1724. doi: 10.1245/s10434-010-1024-1
[26]
Metindir J, Dilek GB, Pak I (2008) Staining characterization by immunohistochemistry of tumor cancer antigen in patients with endometrial cancer. Eur J Gynaecol Oncol 29: 489–492.
[27]
Mahmoudi S, Henriksson S, Farnebo L, Roberg K, Farnebo M (2011) WRAP53 promotes cancer cell survival and is a potential target for cancer therapy. Cell Death Dis 2: e114. doi: 10.1038/cddis.2010.90
[28]
Han Y, Wei F, Xu X, Cai Y, Chen B, et al. (2002) Establishment and comparative genomic hybridization analysis of human esophageal carcinomas cell line EC9706. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 19: 455–457.
[29]
CICAMS (1976) Establishment of an epithelial cell line from human esophageal carcinoma. Chin Med J (Engl). 2: 357–364.
[30]
Tycowski KT, Shu MD, Kukoyi A, Steitz JA (2009) A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles. Mol Cell 34: 47–57. doi: 10.1016/j.molcel.2009.02.020
[31]
Schildkraut JM, Goode EL, Clyde MA, Iversen ES, Moorman PG, et al. (2009) Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer. Cancer Res 69: 2349–2357. doi: 10.1158/0008-5472.can-08-2902
