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