MicroRNA‐577/EIF5A2 axis suppressed the proliferation of DDP‐resistant nasopharyngeal carcinoma cells by blocking TGF‐β signaling pathway

Abstract

AbstractDiaminodichoroplatinum (DDP) resistance of tumor cells is the culprit of nasopharyngeal carcinoma (NPC) treatment failure. MicroRNA‐577 is lowly expressed in NPC tissues, but relevant mechanism is poorly studied. Therefore, this study investigated the role of microRNA‐577 in NPC cells with DDP resistance and its mechanism. DDP‐resistant NPC cells were established by treatment with DDP at increased concentrations (2, 4, 6, 8, or 10 μg/mL). MicroRNA‐577 and EIF5A2 mRNA expressions were detected by qRT‐PCR. Cell biological behaviors were assessed via cell function experiments. Expressions of epithelial mesenchymal transformation (EMT)‐related proteins were quantified by western blot. The targeting relationship between eukaryotic translation initiation factor 5A2 (EIF5A2) and microRNA‐577 was verified through dual‐luciferase reporter assay. The tumor volume and weight were measured after subcutaneous tumorigenesis in mice. As observed from the results, microRNA‐577 expression was reduced in NPC cells and DDP‐resistant NPC cells. Up‐regulated microRNA‐577 suppressed the malignant behaviors and EMT of DDP‐resistant NPC cells, and facilitated cell apoptosis. MicroRNA‐577 targeted EIF5A2, and overexpressed EIF5A2 reversed the above effects of up‐regulated microRNA‐577 on DDP‐resistant NPC cells. Besides, EIF5A2 positively regulated TGF‐β signaling pathway, and TGF‐β treatment offset the promoting effects of EIF5A2 silencing on apoptosis of DDP‐resistant NPC cells. Up‐regulated microRNA‐577 suppressed the proliferation of DDP‐resistant NPC cells, and down‐regulated the levels of EIF5A2 and TGF‐β as well as EMT in vivo. Collectively, microRNA‐577/EIF5A2 axis hinders the EMT progression through the blockage of TGF‐β signaling pathway, so as to inhibit the proliferation of DDP‐resistant NPC.