Abstract
BackgroundMicroRNAs, as small non-coding RNAs, play an important role in tumorigenesis. MiR-483-5p was found to have a significant increase as a diagnostic biomarker of nasopharyngeal carcinoma (NPC), not only in plasma from NPC patients but also in tumor cell lines and biopsy tissues in our previous study. However, its function and mechanism in NPC are still unclear.MethodsTissue microarray including 178 primary NPC and 35 adjacent non-cancerous nasopharyngeal mucosal tissues was used to further validate the overexpression of miR-483-5p. Wound healing and invasion assays were conducted to verify its biological function. RNA sequencing (RNA-seq) and dual-luciferase reporter assay was performed to explore its target, and it was verified in fresh biopsy tissues from 23 NPC patients and 9 patients with chronic nasopharyngitis.ResultsMiR-483-5p was highly expressed in NPC tissues than in adjacent non-cancerous tissues. It was found to have a significant correlation with poor overall survival (OS) [hazard ratio (HR) = 2.89, 95% confidence interval (CI) = 1.00–8.35, p = 0.041] and progression-free survival (PFS) (HR = 1.95, 95%CI = 1.06–3.60, p = 0.029) of NPC patients. Silencing of its expression inhibited the migratory and invasive capacities of NPC cells in vitro. EGR3 (early growth response 3) was identified as a direct target, and inhibiting miR-483-5p expression markedly enhanced the expression of EGR3 at both the mRNA and protein levels. Besides, a significant decrease of EGR3 expression was found in fresh biopsy tissues from NPC patients, in contrast to miR-483-5p expression. Furthermore, directly decreasing the expression of EGR3 could enhance the migration and invasion of NPC cells.ConclusionThe newly identified miR-483-5p/EGR3 pathway provides further insights into the development and metastasis of NPC and may provide a potential therapeutic target for NPC treatment in order to improve survival of NPC patients.
Highlights
Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy
Overexpression of miR-483-5p Was Associated With Poor Prognosis in NPC Patients
High expressions of miR-483-5p were found in the plasma, tumor cell lines, and frozen tumor tissues from NPC patients in our previous study
Summary
Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy. The highest incident of NPC is found in southern China and southeastern Asia, where the annual incidence is about 20–50 cases per 100,000 people [1, 2]. Previous studies have demonstrated that genetic susceptibility, endemic environmental factors, and Epstein–Barr virus (EBV) infection constitute the three etiological contributors to NPC [3]. There is a great need to fully disclose the molecular mechanism underlying the recurrence and metastasis of NPC. MiR-483-5p was found to have a significant increase as a diagnostic biomarker of nasopharyngeal carcinoma (NPC), in plasma from NPC patients and in tumor cell lines and biopsy tissues in our previous study. Its function and mechanism in NPC are still unclear
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