Abstract A02: The feedback loop among miR-449b-3p/ADAM17/NF-κB promotes metastasis in nasopharyngeal carcinoma

Abstract

Abstract Emerging pieces of evidence have proved an important role of miRNAs in tumorigenesis and progression. However, the function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. Quantitative reverse transcription-polymerase chain was used to detect the expression level of miR-449b-3p in NPC cell lines and tissues. We performed cell viability assay, colony formation, flow cytometric, transwell assay, and wound-healing assay to assess the ability of cell proliferation, apoptosis, invasion, and migration in vitro, respectively. NPC xenograft tumor and lymph node metastatic mice model were conducted to validate the function of miR-449b-3p in vivo. Luciferase reporter assay, ChIP assay, and Western blot analysis were actualized to explore the mechanism underlying the miR-449b-3p on NPC metastasis. Here we showed that miR-449b-3p was downregulated in NPC specimens (p<0.001) and cells (p<0.05), and most of the patients with advanced-stage NPC had an impaired expression of miR-449b-3p, on the contrary, early-stage NPC patients had a high level of miR-449b-3p (p<0.001). Moreover, miR-449b-3p inhibited NPC metastasis both in vitro and in vivo. Further investigation revealed that a disintegrin and metalloproteinase 17 (ADAM17) was the direct target of miR-449b-3p. Rescue experiments suggested that the downregulation of ADAM17 in miR-449b-3p inhibited cells partially reversed the inhibition of cell invasion and migration. We also found that ADAM17 could conversely suppress the promoter activity and expression of miR-449b-3p via inducing NF-κB transcriptional activity. In conclusion, our study provides new insights into the mechanism underlying the invasion and metastasis in NPC. The novel miR-449b-3p/ADAM17/NF-κB feedback loop in NPC could potentially be a target for clinical treatment in NPC. Citation Format: Qian Fei, Ming-Yu Du, Ning Jiang, Li Yin, Xia He. The feedback loop among miR-449b-3p/ADAM17/NF-κB promotes metastasis in nasopharyngeal carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A02.