Nei endonuclease VIII-like 2 gene rs8191670 polymorphism affects the sensitivity of non-small cell lung cancer to cisplatin by binding with MiR-548a

Abstract

Background: Nei endonuclease VIII-like 2 (NEIL2) is a gene encoding DNA repair enzyme, which is involved in the base excision repair (BER) pathway in mammalian cells. Cisplatin is a common cytotoxic anti-tumor agent in clinic by destroying normal structure of DNA and inducing cell apoptosis. However, how NEIL2 affects the sensitivity of NSCLC to cisplatin is still unclear. Methods: The clinical data from 206 patients diagnosed pathologically were collected. The DNA sequencing of NEIL2 gene 3'UTR and the PFS curve of NSCLC patients receiving cisplatin-based chemotherapy were performed. Western blot analysis and immunohistochemistry were used to detect NEIL2 protein expression. Human NSCLC cell lines A549 and H1299 were cultured and evaluated for cell viability. RT-PCR was performed for quantitative detection of miR-548a. 3′UTR reporter plasmid was constructed and luciferase reporter assay was used to verify the target gene regulated by miR-548a. Results: In this study, we found that the Neil2 gene had the polymorphism (T/C) in rs8191670 and it is associated with the PFS of advanced NSCLC patients. MiR-548a targets NEIL2 3'UTR to suppress its expression. Upregulation of NEIL2 expression or downregulation of miR-548a could reduce the sensitivity of NSCLC cells to cisplatin. Conclusion: Our results demonstrated that NEIL2 gene rs8191670 polymorphism affects the PFS of advanced NSCLC patients, and the underlying molecular mechanisms may be that miR-548a can regulate NEIL2 expression by binding to its 3'UTR seed region containing rs8191670.