ELF1 suppresses autophagy to reduce cisplatin resistance via the miR‐152‐3p/NCAM1/ERK axis in lung cancer cells

Abstract

AbstractResistance to chemotherapeutic drugs limits the efficacy of chemotherapy in non–small cell lung cancer (NSCLC). Autophagy is an essential mechanism which involves in drug resistance. Our previous research has revealed that miR‐152‐3p represses NSCLC progression. However, the mechanism of miR‐152‐3p in autophagy‐mediated chemoresistance in NSCLC remains unclear. Cisplatin‐resistant cell lines (A549/DDP and H446/DDP) were transfected with related vectors and subjected to cisplatin, autophagy inhibitor, activator, or extracellular signal–regulated kinase (ERK) activator. Flow cytometry, CCK8 and colony formation assays were performed for testing apoptosis and cell viability. The related RNAs or proteins were detected by qRT‐PCR or Western blot. Chromatin immunoprecipitation, luciferase reporter assay or RNA immunoprecipitation were used for validating the interaction between miR‐152‐3p and ELF1 or NCAM1. Co‐IP verified the binding between NCAM1 and ERK. The role of miR‐152‐3p in cisplatin resistance of NSCLC was also validated in vivo. The results showed that miR‐152‐3p and ELF1 were decreased in NSCLC tissues. miR‐152‐3p reversed cisplatin resistance by inhibiting autophagy through NCAM1. NCAM1 promoted autophagy through the ERK pathway and facilitated cisplatin resistance. ELF1 positively regulated miR‐152‐3p level by directly interacting with miR‐152‐3p promoter. miR‐152‐3p targeted NCAM1 to regulate NCAM1 level and then affected the binding of NCAM1 to ERK1/2. ELF1 inhibited autophagy and reversed cisplatin resistance through miR‐152‐3p/NCAM1. miR‐152‐3p inhibited autophagy and cisplatin resistance of xenograft tumor in mice. In conclusion, our study revealed that ELF1 inhibited autophagy to attenuate cisplatin resistance through the miR‐152‐3p/NCAM1/ERK pathway in H446/DDP and A549/DDP cells, suggesting a potential novel treatment strategy for NSCLC.