4.6 Article

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

Journal

CELL CYCLE
Volume 11, Issue 4, Pages 785-796

Publisher

TAYLOR & FRANCIS INC
DOI: 10.4161/cc.11.4.19228

Keywords

nasopharyngeal carcinoma; PTEN; miRNA; miR-205; radioresistance

Categories

Funding

  1. NIHRO1CA [089266]
  2. Cancer Center [CA16672]
  3. National Natural Science Foundation of China [30670627, 30870745, 81071837]
  4. National Natural Science Foundation of Guangdong Province, China [9251008901000005, 06021210]
  5. Sun Yat-Sen University, China
  6. University of Texas MD Anderson Cancer Center

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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.

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