MicroRNA-153-3p regulates cell proliferation and cisplatin resistance via Nrf-2 in esophageal squamous cell carcinoma

Abstract

Background: Our recent studies have indicated that miR-153-3p is downregulated in the esophageal squamous cell carcinoma (ESCC) cell lines and tissues. Upregulation of miR-153-3p was found to inhibit migration and invasion of ESCC cells. However, whether miR-153-3p regulates the cisplatin sensitivity in ESCC cells remains unclear. In this study, we explored whether and how miR-153-3p regulates the proliferation and confers cisplatin resistance in ESCC by targeting the Nrf-2 protein. Methods: Eca109 cell line was transfected with microRNA-153-3p mimics or Nrf-2siRNA and cell proliferation and cisplatin resistance were studied. A dual-luciferase reporter assay was performed on Eca109 cells cotransfected with the wild-type/mutant 3′UTR sequences of Nrf-2 and control or microRNA-153-3p mimics. We determined the correlation between microRNA-153-3p and Nrf-2 expression in human ESCC samples and explored the effect of Nrf-2 in the overall survival rate of ESCC patients. Results: MiR-153-3p significantly suppressed cell proliferation and increased the sensitivity of Eca-109 cells to cisplatin. MiR-153-3p showed a negative correlation with Nrf-2 in human esophageal carcinoma tissues. MiR-153-3p suppressed the expression of Nrf-2 via binding to its 3′-UTR region. Furthermore, inhibition of Nrf-2 also decreased cell proliferation and increased the sensitivity of Eca109 cells to cisplatin. High expression of Nrf-2 in human ESCC samples was associated with poor overall survival of ESCC patients. Conclusion: MiR-153-3p inhibits cell proliferation and confers cisplatin resistance by downregulating Nrf-2 expression in Eca-109 cells. Thus, miR-153-3p/Nrf-2 may play an important role in conferring cisplatin resistance in ESCC. Nrf-2 appears to be a promising therapeutic target for ESCC.