MiR-205 determines the radioresistance of human nasopharyngeal carcinoma by directly targeting PTEN

作者：Changju Qu, Zhihui Liang, Jia-Ling Huang, Ruiying Zhao, Chun-Hui Su, Sumei Wang, Xudan Wang, Rong Zhang, Mong‐Hong Lee, Huiling Yang · 发表于：Cell Cycle · 年份：2012 · DOI：10.4161/cc.11.4.19228 · 被引用次数：181 · 研究领域：MicroRNA in disease regulation、Cancer-related molecular mechanisms research、PI3K/AKT/mTOR signaling in cancer

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.