Effect of EGR1-Mediated LncRNA HOTAIR on MRP1 Gene Expression and MDR in Lung Cancer

Abstract

Background: Multi-drug resistance-associated protein 1 (MRP1) plays critical roles in the multi-drug resistance (MDR) of cancer cells, and its expression is regulated by several transcription factors. However, the effects of EGR1 on MRP1 expression and MDR in lung cancer cells remain unknown.Methods: The expression of Transcription factors EGR1 and lncRNA HOTAIR in Non-small cell lung cancer were detected by using qRT-PCR, at the same time, Western Blot was used to detect the expression of transcription factor EGR1. MTT assay, Flow Cytometry and Observation with laser confocal microscope assay were used to explore the role of EGR1 and lncRNA HOTAIR in Non-small cell lung cancer cells. ChIP PCR assay and Luciferase reporter assays were used to demonstrate the molecular biological mechanism of EGR1 and lncRNA HOTAIR in Non-small cell lung cancer.Results: We found that EGR1 could bind to the MRP1 promoter at site -53/-42 bp and thereby regulate MRP1 expression. EGR1 knock-down reduced MRP1 expression, while EGR1 overexpression increased it. Knockdown of EGR1 increased the drug sensitivity to 5-Fluorouracil (5-FU), Toosendanin (TSN), and cisplatin (DDP), reduced the efflux ability of Rho-123, and induced apoptosis of drug-resistant lung cancer cells A549/DDP, while EGR1 overexpression had the opposite effects. Further, we demonstrated that lncRNA HOTAIR mediated the effects of EGR1 on MRP1 and MDR via sponging of miR-6807-3p. Moreover, we showed that miR-6807-3p exerts its function by targeting the EGR1 3'UTR. Conclusions: We revealed the role and molecular mechanisms of the novel HOTAIR/miR-6807-3p/EGR1 axis in the regulation of MRP1 expression and MDR in lung cancer cells. Our findings identify EGR1 as a potential biomarker and therapeutic target for MDR in human lung cancer.