Abstract
Purpose: Snail-1 is a transcription factor, which takes part in EMT, a process related to the emergence of invasion and cancer progression. The purpose of this study was to evaluate the effect of Snail-1 silencing on the human esophageal squamous cell carcinoma cell line, namely TE-8, in vitro.Methods: In this study, transfection of Snail-1 specific siRNA was conducted into TE-8 cells. The relative mRNA expression levels of Snail-1, Vimentin, CXCR4 and MMP-9 and transcription levels of miR-34a and let-7a were investigated by quantitative Real-time PCR. Western blotting was carried out to evaluate the Snail-1 protein level. Migration assay of TE-8 cells was also performed following the presence or absence of Snail-1 specific siRNA. MTT and TUNEL assays were performed to evaluate cell viability after Snail-1 silencing.Results: It was found that treatment of cancer cells with the Snail-specific siRNA effectively downregulated the expression of Snail-1 in both mRNA and protein levels, and vimentin, CXCR4, and MMP-9 in mRNA level. However, it elevated the transcript levels of miR-34a and let-7a expressions. Furthermore, transfection of cancer cells with the Snail-specific siRNA significantly induced apoptosis in TE8 cells. Moreover, suppression of Snail-1 led to diminished cell migration.Conclusion: It seems that Snail-specific siRNA can significantly interrupt esophageal cancer cell migration and reduce metastatic-related factors and induce miR-34a and let-7a in vitro. The bottom line is that therapeutic approaches via targeting Snail-1 can be used for ESCC treatment, suggesting that other possible target molecules for ESCC therapy require to be explored.
Highlights
Esophageal cancer (EC) is considered as the eighth prevalent and the sixth most lethal tumor in the world.[1]
The Snail-1 specific small interference RNA (siRNA) down-regulated Snail-1 mRNA in human esophageal squamous cell carcinomas (ESCC) cell line, TE-8 After exposure to Snail-1 siRNA, TE-8 cells were evaluated by Quantitative RT-PCR analysis (qRT-PCR) in 24, 48 and 72 h after transfection
Through blocking Snail, cancer cell metastasis can be interrupted through impairing with the processes, such as epithelial-mesenchymal transition (EMT) and invasive property
Summary
Esophageal cancer (EC) is considered as the eighth prevalent and the sixth most lethal tumor in the world.[1]. The EAC phenotype is almost 50% more common than ESCC in the United States, while it has been reported to be about 20-times less prevalent in Asians.[1,3] ESCC remains the main subtype of EC in China; EAC is the most prevalent form of EC in Western populations.[1] In spite of recent advancements in surgical techniques, enhanced imaging, and novel chemotherapeutic agents, our apprehension of the disease remains poor, which in part is related to the early invasive and metastatic characteristics of EC cells.[4] As a consequence, it is paramount to investigate the mechanisms of invasion and metastasis of ESCC. Snail-1 belongs to the Snail superfamily of zinc-finger transcription factors, which consist of Snail-2 (Slug) and Snail-3 (Smuc) proteins. This superfamily exerts a function in the survival and differentiation of various cells, which are the two major processes in the mechanobiology of cancers. Chromosome 20q13.2 harbors snail family transcriptional repressor 1 (SNAI1) gene, which codifies a protein consisting of 264 amino acids that exerts transcriptional repressor
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