MicroRNA-483-5p Predicts Poor Prognosis and Promotes Cancer Metastasis by Targeting in Nasopharyngeal Carcinoma.

BACKGROUND

MicroRNAs, 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.

METHODS

Tissue 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.

RESULTS

MiR-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,  = 0.041] and progression-free survival (PFS) (HR = 1.95, 95%CI = 1.06-3.60,  = 0.029) of NPC patients. Silencing of its expression inhibited the migratory and invasive capacities of NPC cells . (early growth response 3) was identified as a direct target, and inhibiting miR-483-5p expression markedly enhanced the expression of at both the mRNA and protein levels. Besides, a significant decrease of expression was found in fresh biopsy tissues from NPC patients, in contrast to miR-483-5p expression. Furthermore, directly decreasing the expression of could enhance the migration and invasion of NPC cells.

CONCLUSION

The newly identified miR-483-5p/ 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.