Exosomal miR-18a-5p promotes EMT and metastasis of NPC cells via targeting BTG3 and activating the Wnt/β-catenin signaling pathway

Abstract

This study investigated the underlying mechanism of miR-18a-5p regulating the proliferation, invasion, and metastasis of nasopharyngeal carcinoma (NPC) cells in vitro and in vivo to indicate the pathogenesis of NPC. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was utilized to determine miR-18a-5p expression level in NPC tissues and cell lines. Besides, 2,5-diphenyl-2 H-tetrazolium bromide (MTT) and colony formation assays were employed to detect the effect of miR-18a-5p expression level on NPC cell proliferation. Wound healing and Transwell assays were utilized to detect the effect of miR-18a-5p on NPC cell invasion and migration. The expression levels of epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin, and E-cadherin) were identified by Western blot assay. After collecting exosomes from CNE-2 cells, it was found that exosomal miR-18a-5p secreted from NPC cells promoted NPC cell proliferation, migration, invasion, and EMT, whereas inhibition of miR-18a-5p expression level led to the opposite results. The dual-luciferase reporter assay showed that BTG anti-proliferation factor 3 (BTG3) was the target gene of miR-18a-5p, and BTG3 could overturn the effect of miR-18a-5p on NPC cells. Xenograft mouse model of NPC nude mice showed that miR-18a-5p promoted NPC growth and metastasis in vivo. This study revealed that exosomal miR-18a-5p derived from NPC cells promoted angiogenesis via targeting BTG3 and activating the Wnt/β-catenin signaling pathway.