MIR-499 Enhances the Cisplatin Sensitivity of Esophageal Carcinoma Cell Lines by Targeting DNA Polymerase β

Abstract

Background: Human DNA polymerase β (DNA polymerase β, polβ) is a small monomeric protein essential for short-patch base excision repair (BER). It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. Methods: Luciferase reporter and western blot assays were used to determine whether polβ is a major target of MIR-499. CCK-8, colony-forming survival and in vivo tumor growth assays were conducted to evaluate if MIR-499 can potentially enhance the cisplatin sensitivity and therefore inhibit the proliferation of esophageal cancer (EC) cells. Flow cytometry and immunofluorescence microscopy assays were performed to evaluate whether MIR-499 enhance the cisplatin sensitivity and the corresponding apoptosis in EC cells. Results: polβ was pinpointed as a target gene of MIR-499. Additionally, we identified that MIR-499 can enhance cisplatin's function of inhibiting proliferation and of promoting apoptosis in EC9706 and KYSE30 cell lines. Conclusions: We first investigated whether MIR-499 modulates polβ, and observed the influence of MIR-499 up-regulation on the sensitivity of EC cell lines to cisplatin treatment. Our study paves the way for more insightful understanding and application of chemotherapy in esophageal cancer in the future.