Abstract
BackgroundEsophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable. MicroRNA (miR) is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC.MethodsTotal RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT)-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR.ResultsBased on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold) in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2, accompanied by reduction of E-cadherin, a regulator of epithelial mesenchymal transition. The miR-205 expression levels were not associated with histological differentiation of human ESCC.ConclusionsThese results imply that miR-205 is an ESCC-specific miR that exerts tumor-suppressive activities with EMT inhibition by targeting ZEB2.
Highlights
Esophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable
2-fold) overexpressed in both ESCC cell lines compared to non-malignant Het-1A cells (Figure 1A)
MiR-153, -100, -125b, -10a, -99a, -376a, -379, -651, and -146b were significantly lower in expression in the two ESCC cell lines than in Het-1A cells (Figure 1B)
Summary
Esophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. Barrett’s adenocarcinoma is the most rapidly increasing cancer in Western countries [2], esophageal squamous cell carcinoma (ESCC) is still dominant in East Asia, including Japan [3]. Accumulating evidence indicates that deregulation of miRs is associated with human malignancies and suggests a causal role of miRs in tumor initiation and progression, since they can function as oncogenes or tumor suppressors [10]. Previous studies showed distinct differences in miR expression patterns between squamous cell carcinoma and adenocarcinoma in esophageal and other cancers [3,11,12]. There has been little information on the functional roles of miRs specific for ESCC [14]
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