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Snail-1 Silencing by siRNA Inhibits Migration of TE-8 Esophageal Cancer Cells Through Downregulation of Metastasis-Related Genes.

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.

SUBMITTER: Hemmatzadeh M

PROVIDER: S-EPMC6156482 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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Snail-1 Silencing by siRNA Inhibits Migration of TE-8 Esophageal Cancer Cells Through Downregulation of Metastasis-Related Genes.

Hemmatzadeh Maryam M Mohammadi Hamed H Babaie Farhad F Yousefi Mehdi M Ebrazeh Mehrdad M Mansoori Behzad B Shanehbandi Dariush D Baradaran Behzad B

Advanced pharmaceutical bulletin 20180829 3

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 tran ...[more]

PMID: 30276140

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Project description:The present study identified that fibroblast growth factor receptor 3 (FGFR3) was significantly upregulated in bone metastasis of lung adenocarcinoma. RNA interference (RNAi) is a powerful approach for treating a wide range of human diseases, including cancer, through downregulating the expression of selected genes. In the present study, the invasiveness of A549 cells cultured in vitro was altered by small interfering (si)RNA targeting FGFR3, and the regulatory effect of silencing FGFR3 on the expression levels of E-cadherin and matrix metalloproteinase (MMP)9 was investigated. Human lung adenocarcinoma A549 cells were transfected with synthetic specific siRNAs targeting a fragment of the FGFR3 gene (namely, siRNA-855, siRNA-1447 and siRNA-2076) or with negative control (NC) siRNA. Cells were divided into five groups (A, siRNA-855 group; B, siRNA-1447 group; C, siRNA-2076 group; D, NC-siRNA group; and E, blank control group). The effect of the above siRNAs targeting FGFR3 on the invasion capacity of A549 cells was detected by Transwell assay. siRNAs against FGFR3 were transfected into A549 cells with by Lipofectamine® 2000, and the expression levels of FGFR3, E-cadherin and MMP9 were measured by reverse transcription-quantitative polymerase chain reaction and western blot assay. The experimental findings indicated that the expression levels of FGFR3 and MMP9 were significantly reduced in the siRNA-FGFR3-transfected groups (A-C groups), compared with those in the D and E groups (P<0.01). In addition, the expression levels of E-cadherin were markedly elevated in the A-C groups, compared with those in the D and E groups (P<0.01). There was no significant difference in E-cadherin expression between the A-C groups, or between the D and E groups (P>0.05). These results indicated that siRNA-FGFR3 was able to decrease the invasiveness of A549 cells, inhibit the expression of MMP9 and increase the expression of E-cadherin by downregulating the expression of FGFR3. Taken together, the results of the present study indicated that the upregulation of E-cadherin expression and the downregulation of MMP9 expression are able to inhibit the migration of A549 cells, and siRNA silencing FGFR3 acts as a tumor suppressor in these cells.

Dataset Information

Snail-1 Silencing by siRNA Inhibits Migration of TE-8 Esophageal Cancer Cells Through Downregulation of Metastasis-Related Genes.

Publications

Snail-1 Silencing by siRNA Inhibits Migration of TE-8 Esophageal Cancer Cells Through Downregulation of Metastasis-Related Genes.

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