miR-24对鼻咽癌放射敏感性的影响

Effect of miR-24 on radiosensitivity of nasopharyngeal carcinoma

目的:探讨miR-24在鼻咽癌中的表达和对鼻咽癌细胞放射敏感性的影响。方法:收集广西医科大学第一附属医院82例鼻咽癌组织及22例正常鼻咽组织,基因芯片筛选鼻咽癌细胞中差异表达的miRNA谱;实时荧光定量PCR(qPCR)技术检测miR-24的表达,分析miR-24的表达水平与临床分期的关系及对疗效的影响。构建鼻咽癌细胞CNE1稳转株及鼻咽癌细胞CNE1miR-24裸鼠模型,MTT实验和克隆形成实验检测实验组(miR-24组)与空白对照组(miR-NC组)鼻咽癌细胞增殖率及不同照射剂量处理后的生存率;单剂量12Gy/f/d局部照射鼻咽癌裸鼠移植瘤后,比较两组裸鼠的肿瘤体积。结果:基因芯片结果显示miR-24表达下调最为明显;miR-24在鼻咽癌细胞CNE1低于正常鼻咽上皮细胞NP69(P<0.01);miR-24在T分期、N分期及临床分期的早期表达较高(P<0.01);低表达miR-24的鼻咽癌患者治疗无效率明显高于高表达患者(P<0.05);体外实验结果显示,与miR-NC组比较,miR-24组细胞增殖率及生存率明显降低(P<0.01或P<0.05);体内实验表明,与miR-NC组比较,照射后miR-24组移植瘤体积明显减小(P<0.001)。结论:过表达miR-24能够抑制鼻咽癌细胞的增殖,增加鼻咽癌细胞的放射敏感性,且高表达miR-24的鼻咽癌患者治疗效果较好。

Objective：To investigate the expression of miR-24 in nasopharyngeal carcinoma （NPC） patients and its effect on radiosensitivity in vitro and in vivo. Methods： The nasopharyngeal tissues from 82 NPC patients and 22 cases of healthy controls were collected and miR-24 expression in these tissues was detected by qPCR. The correlation between the expression of miR-24 and the clinical stage and efficacy was analyzed. The differentially expressed miRNA profiles in NPC ceils were identified by microarray. The NPC CNE1 cells or BALB/C nude mice were divided into a highly-expressed miR-24 group and a control group （miR-NC group）. MTT assay and clone formation assay were used to detect cell proliferation rates and clo- ning efficiency. BALB/C nude mice subjected to NPC were treated with 12 Gy partial irradiation, and the tumor volume was compared between the two groups. Results： Microarray assay results showed that miR-24 expression was significantly downregulated in NPC cells. The expression of miR-24 in NPC tissues was higher than that in controls, and it was correlated with tumor size and clinical stage （ P 〈0.01）. The therapeutic effect in patients with high expression of miR-24 was superior to those with low-expression of miR-24 （ P 〈0.05）. Compared with miR-NC group, the cell proliferation rate, survival rate and the transplanted tumor size were reduced in miR-24 group. Conclusion： Over expressed miR-24 could inhibit the proliferation of NPC cells and enhance radiosensitivity of NPC in vitro and in vivo. The NPC patients with highly-expressed miR-24 had better prognosis.