Recurrent nasopharyngeal carcinoma, which represents a small proportion of head-and-neck cancers, has a unique set of patho-clinical characteristics. The management of recurrent nasopharyngeal carcinoma remains a challenging clinical problem. Traditional treatments offer limited local control and survival benefits; more seriously, they frequently induce severe late complications. Recently, novel treatment techniques and strategies—including precision radiotherapy, endoscopic surgery or transoral robotic resection, third-generation chemotherapy regimens, and targeted therapies and immunotherapy—have provided new hope for patients with recurrent nasopharyngeal carcinoma. Some of these patients can potentially be cured with modern treatments. However, a lack of adequate evidence makes it difficult for clinicians to apply these powerful techniques and strategies. Individualized management guidelines, full evaluation of quality of life in these patients, and a further understanding of the mechanisms underlying recurrence are future directions for research into recurrent nasopharyngeal carcinoma.

Radiotherapy is the standard therapy for nasopharyngeal carcinoma (NPC); however, radioresistance can hinder successful treatment. Here, we report that miR-24 acts as a tumor suppressor and radiosensitizer in NPC cells and xenografts by targeting Jab1/CSN5. Although accumulating evidence has shown that Jab1/CSN5 functions as an oncoprotein in human cancers, its regulation through miRs has not been described. In this study, we found that Jab1/CSN5 functioned in a manner opposite that of miR-24 in NPC tumorigenesis and radioresistance. We demonstrated that miR-24 inhibits Jab1/CSN5 translation via direct binding to its 3’UTR and 5’UTR, leading to tumor growth inhibition, and sensitizes NPC tumors to radiation in vivo. Furthermore, silencing Jab1/CSN5 phenocopied the function of miR-24 in NPC cells after ionizing radiation treatment, resulting in increased apoptosis. Finally, we analyzed 50 paired samples of primary and matched recurrent NPC tissues from 25 NPC patients and subjected them to high-throughput genomic quantitative nuclease protection assay for quantifying simultaneously miR and mRNA levels. Our results showed that miR-24 levels were significantly decreased in recurrent NPC and that levels of Jab1/CSN5, as its target, were higher than those in primary NPC. Together, our findings indicate that miR-24 inhibits NPC tumor growth and increases NPC radiosensitivity by directly regulating Jab1/CSN5 and that both miR-24 and Jab1/CSN5 can serve as prognostic markers for NPC recurrence; this, in turn, may provide a promising therapeutic strategy for reversing NPC radioresistance.