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MicroRNA221 and -222 Regulate Radiation Sensitivity by Targeting the PTEN Pathway

MicroRNA221 and -222 Regulate Radiation Sensitivity by Targeting the PTEN Pathway,10.1016/j.ijrobp.2010.12.049,International Journal of Radiation Onco

MicroRNA221 and -222 Regulate Radiation Sensitivity by Targeting the PTEN Pathway  
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Chunzhi Zhang, Chunsheng Kang, Ping Wang, Yongzhen Cao, Zhonghong Lv, Shizhu Yu, Guangxiu Wang, Anling Zhang, Zhifan Jia, Lei Han, Chunying Yang, Hiromichi Ishiyamahttp://academic.research.microsoft.com/io.ashx?type=5&id=49347562&selfId1=0&selfId2=0&maxNumber=12&query=
Purpose: MicroRNAs (miRNAs) are noncoding RNAs inhibiting expression of numerous target genes by posttranscriptional regulation. miRNA-221 and miRNA-222 (miRNA-221/-222) expression is elevated in radioresistant tumor cell lines; however, it is not known whether and how miRNAs control cellular responses to ionizing irradiation. Methods and Materials: We used bioinformatic analyses, luciferase reporter assay, and genetic knockdown and biochemical assays to characterize the regulation pathways of miRNA-221/-222 in response to radiation treatment. Results: We identified the PTEN gene as a target of miRNA-221/-222. Furthermore, we found that knocking down miRNA-221/-222 by antisense oligonucleotides upregulated PTEN expression. Upregulated PTEN expression suppressed AKT activity and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in tumor cells. Conclusions: miRNA-221/-222 control radiation sensitivity by regulating the PTEN/AKT pathway and can be explored as novel targets for radiosensitization.
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