miR-421下调FOXO4增强鼻咽癌细胞CNE-2放疗敏感性

Downregulation of FOXO4 by miR-421 Enhances the Radiosensitivity of Nasopharyngeal Carcinoma Cell CNE-2

鼻咽癌(nasopharyngeal carcinoma,NPC)在头颈部肿瘤中位居首位,对人们的身体健康构成严重威胁。放射治疗是目前治疗鼻咽癌的有效手段,但是鼻咽癌组织存在对放射射线不敏感的细胞,这对放疗敏感性提出了更高要求。为探究miR-421下调FOXO4对鼻咽癌细胞CNE-2放疗敏感性的作用,本研究先对miR-421靶基因进行预测,然后考察不同放疗剂量对miR-421和FOXO4 mRNA表达水平的影响,直接证明miR-421及FOXO4与鼻咽癌细胞放疗敏感性有关,最后通过存活曲线、流式细胞仪检测、MTT法,探究了miR-421上调、FOXO4沉默对鼻咽癌细胞CNE-2放疗敏感性的影响。结果发现,FOXO4为miR-421的潜在靶基因,鼻咽癌细胞CNE-2经放射处理后,miR-421的表达水平明显下降,FOXO4的表达水平显著升高;miR-421上调和FOXO4沉默均增强了鼻咽癌细胞放疗的敏感性,降低了癌细胞存活率和克隆形成率,提高了的癌细胞凋亡率。可得知,miR-421通过负调控FOXO4靶基因增强鼻咽癌细胞CNE-2放疗的敏感性,这为进一步深入研究miR-421对其靶基因FOXO4的作用机制打下基础。

ENasopharyngeal carcinoma （NPC） occupies the dominant position in head and neck neoplasms, which poses a serious threat to people＇s physical health. Radiotherapy is an effective method for the treatment of nasopharyngeal carcinoma, but there are cells in the nasopharyngeal carcinoma tissues that are not sensitive to radiation-ray, which puts forward higher requirements on radiosensitivity. To investigate the effect of downregulation of FOXO4 by miR-421 on the radiosensitivity of nasopharyngeal carcinoma cell CNE-2, this study first predicted the miR-421 target gene, and then explored the effect of different radiotherapy dose on the expression level of mir-421 and FOXO4 mRNA, which directly demonstrate that miR-421 and FOXO4 were related with the radiosensitivity of nasopharyngeal carcinoma cells. Finally, survival curve, flow cytometry detection and MTT method were applied to detect the influence ofupregulation ofmiR-421 and FOXO4 silencing on the radiosensitivity of nasopharyngeal carcinoma cell CNE-2. The results showed that FOXO4 was the potential target gene of miR-421. When nasopharyngeal carcinoma CNE-2 cell was treated by radiation, the expression level of miR-421 decreased significantly, but the expression level of FOXO4 significantly increased： Upregulation of miR-421 and FOXO4 silencing both enhanced the radiosensitivity of nasopharyngeal carcinoma cells, decreased the cancer cell survival rate and cloning efficiency, and improved apoptosis rate of cancer cells. All these indicated that miR-421 negatively regulated the expression of FOXO4 gene to enhance the radiosensitivity of nasopharyngeal carcinoma cell CNE-2, which laid the foundation for the further study about the functional mechanism of miR-421 on its target gene FOX04.