MicroRNA-221 和 -222 通过靶向 PTEN 通路调节辐射敏感性。
MicroRNA-221 and -222 regulate radiation sensitivity by targeting the PTEN pathway.
机构信息
Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin 300052, China.
出版信息
Int J Radiat Oncol Biol Phys. 2011 May 1;80(1):240-8. doi: 10.1016/j.ijrobp.2010.12.049.
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.
目的
MicroRNAs (miRNAs) 是一类非编码 RNA，可以通过转录后调控抑制大量靶基因的表达。miRNA-221 和 miRNA-222（miRNA-221/-222）在耐辐射肿瘤细胞系中表达上调；然而，尚不清楚 miRNAs 是否以及如何控制细胞对电离辐射的反应。
方法和材料
我们使用生物信息学分析、荧光素酶报告基因检测、基因敲低和生化检测来研究 miRNA-221/-222 在辐射处理下的调控途径。
结果
我们鉴定出 PTEN 基因为 miRNA-221/-222 的靶基因。此外，我们发现反义寡核苷酸敲低 miRNA-221/-222 会上调 PTEN 的表达。上调的 PTEN 表达抑制了 AKT 的活性，增加了辐射诱导的细胞凋亡，从而增强了肿瘤细胞的放射敏感性。
结论
miRNA-221/-222 通过调节 PTEN/AKT 通路来控制辐射敏感性，可作为放射增敏的新靶点进行探索。
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