MiR-128–3p increases the radiosensitivity in nasopharyngeal carcinoma via regulating vascular endothelial growth factor C

Abstract

PurposeThis study aims to investigate the role of miR-128–3p in the radiosensitivity of nasopharyngeal carcinoma (NPC) and its underlying mechanism. Methods6–10B cells were transfected with miR-128–3p mimic, pcDNA-VEGFC, and the corresponding negative control. C666–1 cells were transfected with miR-128–3p inhibitor, sh-VEGFC, and the corresponding negative control. RT-qPCR was used to determine the miR-128–3p and VEGFC mRNA expression level. Dual-luciferase assay was used to investigate the relationship between miR-128–3p and VEGFC. The protein levels of VEGFC, H2AX, γ-H2AX, p-P50, p-P65, p-IκB, and the apoptosis markers Bcl-2, caspase3, caspase9, and Bax were detected by Western blot. The proliferation activity was detected by CCK-8, and cell DNA damage was assessed by comet assay. The apoptosis rate was detected by flow cytometry. The growth of NPC in vivo was observed in mice through xenotransplantation. TUNEL staining was used to detect cell apoptosis in tumor tissues. ResultsmiR-128–3p was targeted and was negatively regulated with VEGFC. Overexpression of miR-128–3p or knockdown VEGFC significantly inhibited the proliferation of 6–10B and C666–1 cells, induced DNA damage and apoptosis and promoted the radiosensitivity of cells. Knocking down miR-128–3p or up-regulated VEGFC promoted the proliferation of C666–1 and 6–10B cells, reduced cell DNA damage and apoptosis, and enhanced cell resistance to radiotherapy. Overexpression of miR-128–3p reversed the effect of VEGFC on 6–10B cells and inhibited P50/P65/IKB signal pathway. In vivo, experiments in mice confirmed that miR-128–3p significantly inhibited NPC proliferation and promoted DNA damage and apoptosis by targeting VEGFC. ConclusionThe miR-128–3p pathway is a novel therapy target to overcome radiation resistance in NPC.