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.
Purpose To determine the supporting role of a novel foldable capsular vitreous body (FCVB) with magnetic resonance imaging (MRI) in the treatment of severe retinal detachment in human eyes. Methods The study examined nine eyes of nine patients. Among the nine eyes, five had suffered penetrating injuries while four had suffered contusions of the eyeball involving large defects of the retina or choroids. A standard three-port pars plana vitrectomy was performed, FCVB was triple-folded and sent into the vitreous cavity; balanced salt solution (BSS) was injected into the capsule to support the retina. Three cardinal axes of nine eyes were examined using MRI at baseline and at the 3-month follow up. Results MRI revealed that the signal intensity of the FCVB was similar to the normal vitreous body, with low-signal intensity on T1-weighted image and high-signal intensity on T2-weighted image. In three pre-operative silicone oil-or heavy silicone oil-filled eyes, FCVBs were not fully inflated, and eyeball deformation was observed in one eye. Shifts of three cardinal axes of three eyes (horizontal, anteroposterior, and vertical) according to MRI, were À4.33, À4.67, and À2.67 mm. In the remaining six eyes, FCVBs were well distributed in the vitreous cavity and evenly supported the retina; the cardinal axes of the eyes were similar to pre-operation. Shifts of three cardinal axes of six eyes were À0.34, À0.34, and À0.34 mm. In a total of nine eyes, shifts of three cardinal axes were À1.67, À1.77, and À1.11 mm. Statistically significant difference showed only between the horizontal axis of nine eyes pre-operatively and post-operativelyConclusion This study demonstrated the effectiveness of MRI to monitor the supporting role of an FCVB in the treatment of severe retinal detachment in human eyes.
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