Mir-25 Promotes Metastasis of Esophageal Cancer by Targeting BTG2

Abstract

At present times, various kinds of literature have suggested the miR-25 acts as an oncogene in various types of human malignancies and until now, very less work has been performed pertaining to the role of miR-25 in esopharyngeal cancer. This study was performed to confirm that miR-25 is overexpressed in esophageal squamous cell carcinoma (ESCC) tumor tissue as a prognostic biomarker and to clarify the mechanism of miR-25. The expression levels of miR-25 and BTG2 were detected in esophageal squamous cell carcinoma tumor tissue. A stably knocked-down miR-25 cell line (miR-25KD) was established in esophageal squamous cell carcinoma cell lines. Moreover, a CCK-8 assay was performed for determining the role of miR-25 in proliferation. The Transwell assays were organized to detect metastasis. Later, a gene profiling study was carried out to identify the gene expression pertaining to tumor progression. The expression of miR-25 in the esophageal cancer tissues was much higher compared with that in paracarcinoma tissues (6.42±4.28 VS 3.36±2.63, p<0.001). A high level of miR-25 was identified to be correlated with postoperative metastasis (χ²=8.187, p =0.004). BTG2 levels were significantly lower in tumor tissues (3.24±2.79) than those in adjacent non-tumor tissues (1.96±1.56 VS 2.64±1.41, p<0.001). Negative signs of BTG2 were also associated with postoperative metastasis (χ²=7.766, p=0.005). Besides, BTG2-negative cancer tissues are often accompanied by increased miR-25 expression levels (χ²=18.379, p<0.001). Patients with high miR-25 levels were found with worse overall survival (OS) (χ²=6.906, p=0.009) and metastasis-free survival (MFS) (χ²=4.991, p=0.025). Patients with positive BTG2 had better OS (χ²=12.917, p <0.001) and MFS (χ²=14.173, p<0.001). Knockdown of miR-25 helped to inhibit the proliferation and metastatic ability of esophageal cancer cells. Also, MiR-25 inhibits the expression of BTG2 directly. Results also show that miR-25 also helps to suppress the expression of vimentin and increase the expressions of E-cadherin and BTG2. MiR-25 promotes ESCC progression by directly inhibiting the expression of BTG2. MiR-25 and BTG2 can be utilized as prognostic biomarkers.

Keywords: BTG2; E-cadherin; Esopharyngeal cancer; Prognostic biomarker; miR-25.