LncRNA HOTAIR regulates the expression of MRP1 gene through the mir-6807-5p/Egr1 axis to affect the multidrug resistance of lung cancer cells.

Abstract

Multi-drug resistance-associated protein 1 (MRP1) plays critical roles in the multi-drug resistance (MDR) of cancer cells, LncRNA HOTAIR is closely related to MDR in lung cancer, however, the effects of HOTAIR on MRP1 expression and MDR in lung cancer cells (A549/DDP) remain unknown. In this study, the effects of HOTAIR on MRP1 gene expression and MDR in A549/DDP cells were monitored. LncRNA HOTAIR was upregulated in A549/DDP cells, and overexpression of HOTAIR promoted MRP1 expression and MDR development. The opposite trend was observed when HOTAIR was silenced in A549/DDP cells. To uncover the role of LncRNA HOTAIR in the MDR of human lung cancer, the effects of Egr1 on MRP1 gene expression and MDR in A549/DDP cells were monitored. The results showed that Egr1 could bind to the MRP1 promoter at site -53/-42 bp and regulate MRP1 expression. Egr1 knock-down reduced MRP1 expression, while Egr1 overexpression increased it. Further, the results demonstrated that LncRNA HOTAIR mediated the effects of Egr1 on MRP1 and MDR via sponging of miR-6807-3p. Moreover, miR-6807-3p exerts its function by targeting the Egr1 3'UTR. In conclusion, the results revealed the novel HOTAIR/miR-6807-3p/Egr1 axis in the regulation of MRP1 expression and MDR in lung cancer cells.