title: MiR-205 determines the radioresistance of human nasopharyngeal carcinoma by directly targeting PTEN.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Changju
authors.initials: C
authors.lastname: Qu
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liang
authors.forename: JiaLing
authors.initials: J
authors.lastname: Huang
authors.forename: Ruiying
authors.initials: R
authors.lastname: Zhao
authors.forename: Chunhui
authors.initials: C
authors.lastname: Su
authors.forename: Sumei
authors.initials: S
authors.lastname: Wang
authors.forename: Xudan
authors.initials: X
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Mong-Hong
authors.initials: MH
authors.lastname: Lee
authors.forename: Huiling
authors.initials: H
authors.lastname: Yang
mesh_terms: D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D005434:Flow Cytometry; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C534425:MIR205, human; C494929:PTEN protein, human