Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Cell Cycle. 2012 Feb 15;11(4):785-96. doi: 10.4161/cc.11.4.19228.
Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance severely reduces NPC radiocurability. Here, we have established a radio-resistant NPC cell line, CNE-2R, and investigate the role of miRNAs in radioresistance. The miRNAs microarray assay reveals that miRNAs are differentially expressed between CNE-2R and its parental cell line CNE-2. We find that miR-205 is elevated in CNE-2R. A target prediction algorithm suggests that miR‑205 regulates expression of PTEN, a tumor-suppressor. Introducing miR-205 into CNE-2 cells suppresses PTEN protein expression, followed by activation of AKT, increased number of foci formation and reduction of cell apoptosis postirradiation. On the other hand, knocking down miR-205 in CNE-2R cells compromises the inhibition of PTEN and increases cell apoptosis. Significantly, immunohistochemistry studies demonstrate that PTEN is downregulated at late stages of NPC, and that miR-205 is significantly elevated followed the radiotherapy. Our data conclude that miR-205 contributes to radioresistance of NPC by directly targeting PTEN. Both miR-205 and PTEN are potential predictive biomarkers for radiosensitivity of NPC and may serve as targets for achieve successful radiotherapy in NPC.
放射疗法是鼻咽癌(NPC)的主要治疗方法,但放射抵抗严重降低了 NPC 的放射治愈率。在这里,我们建立了一个放射抵抗的 NPC 细胞系 CNE-2R,并研究了 miRNA 在放射抵抗中的作用。miRNA 微阵列分析表明,CNE-2R 与其亲本细胞系 CNE-2 之间的 miRNA 表达存在差异。我们发现 miR-205 在 CNE-2R 中上调。靶预测算法表明 miR-205 调节肿瘤抑制因子 PTEN 的表达。将 miR-205 引入 CNE-2 细胞中会抑制 PTEN 蛋白表达,随后 AKT 激活、焦点形成数量增加和细胞凋亡减少。另一方面,在 CNE-2R 细胞中敲低 miR-205 会破坏对 PTEN 的抑制作用并增加细胞凋亡。重要的是,免疫组织化学研究表明,PTEN 在 NPC 的晚期下调,并且在放射治疗后 miR-205 显著升高。我们的数据得出结论,miR-205 通过直接靶向 PTEN 促进 NPC 的放射抵抗。miR-205 和 PTEN 都是 NPC 放射敏感性的潜在预测生物标志物,可能成为在 NPC 中实现成功放射治疗的靶点。