Abstract

BackgroundEsophageal 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.MethodsWRAP53 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.ResultsExpression 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.ConclusionThis 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.

Highlights

  • Natural antisense transcripts (NATs), called antisense RNAs, are RNAs that contain sequences that are complementary to other endogenous transcripts

  • We investigated the expression of WRAP53 protein and mRNA in Esophageal cancer (EC) cell lines, Esophageal squamous cell carcinoma (ESCC) tumors, and adjacent nonneoplastic esophageal mucosa tissue

  • Expression of WRAP53 in ESCC cell lines To investigate the relationship between WRAP53 expression and ESCC, we first examined the expression of WRAP53 in 4 ESCC cell lines (EC109, EC9706, KYSE150, and KYSE180) we detected the expression of WRAP53 protein in all 4 ESCC cell lines with an expected molecular weight of 75 kDa(Figure 1)

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Summary

Introduction

Natural antisense transcripts (NATs), called antisense RNAs, are RNAs that contain sequences that are complementary to other endogenous transcripts. Investigations into NAT functions have indicated that NATs play key roles in carcinogenesis and the development of cancers [3,4,5,6,7,8,9]. A natural antisense transcript to p53 (WRAP53) has recently been identified; WRAP53 gives rise to p53 antisense transcripts that regulate p53 mRNA expression and are required for p53 activity upon. The natural antisense transcript (NAT) WRAP53 regulates p53 expression and WRAP53 protein is a component of telomerase. NATs play key roles in carcinogenesis, and 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

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