Role of mIR-205/PTEN in cisplatin-resistant esophageal squamous cell carcinoma

Abstract

Purpose: To evaluate the effect of miRNA-205 on cisplatin-resistant TE13 cell lines, and the interaction of miRNA-205 with downstream signaling pathway. Methods: TE13 cells were treated with cisplatin at a concentration of 1.5 μg/mL every 24 h for 3 months. Cisplatin-resistant cell lines were maintained in the continuous presence of 2 μg/ml cisplatin and supplemented every 72 h. Half-maximal inhibitory concentration (IC 50 ) value was determined by MTT assay, and cell apoptosis was tested by flow cytometry. In addition, luciferase reporter assay was conducted to test the binding of miRNA-205 and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) 3’UTR. Results: The cisplatin-resistant (cis-TE13) cell line was well established based on IC 50 values (cis-TE13, IC 50 = 2.215; TE13, IC 50 = 0.304). The levels of miRNA-205, phosphatase, PTEN, and protein kinase B (p-AKT) were abnormally expressed in cis-TE13 cells. Overexpression of miRNA-205 significantly promoted cell viability and decreased cell apoptosis of cis-TE13 cells as indicated by IC 50 values (cis-TE13, IC 50 = 3.537; TE13, IC 50 = 0.580). Moreover, miRNA-205 significantly activated p-AKT expression by inhibiting PTEN expression. In contrast to miRNA-205, PTEN overexpression inhibited cell viability, increased cell apoptosis of cis-TE13 cells (cis-TE13, IC 50 = 2.625; TE13, IC 50 = 0.246), decreased the expression of p-AKT, and counteracted the regulation of miRNA-205 (control, IC 50 = 2.297; miR-205, IC 50 = 4.693; miR-205+PTEN, IC 50 = 2.011). Conclusion: These findings indicate that miRNA-205 exacerbates esophageal squamous cell carcinoma via inhibition of PTEN expression, suggesting the potential value of miRNA-205 in the diagnosis or treatment of esophageal squamous cell carcinoma.