Thoracic Cancer (Mar 2020)
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.
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