Radiation modulation of microRNA in prostate cancer cell lines.
Radiation modulation of microRNA in prostate cancer cell lines.
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DOI：
10.1002/pros.20827
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发表时间：
2008-11-01
期刊：
影响因子：
2.8
通讯作者：
Johnstone, Peter A. S.
中科院分区：
文献类型：
--
作者：
Josson, Sajni;Sung, Shian-Ying;Lao, Kaiqin;Chung, Leland W. K.;Johnstone, Peter A. S.
microRNA（miRNA）是一种基因调控因子，在细胞应激反应中发挥重要作用。使用多重定量实时PCR，我们对前列腺癌细胞对放射治疗的反应进行了整体miRNA筛选。几种miRNA在辐射处理后发生了显著改变。在miR-521和miR-34 c中观察到显著变化。为了确定miR-521在辐射应答中的作用，我们使用miR-521模拟物瞬时过表达miR-521。miR-521模拟物显著地使前列腺癌细胞对放射治疗敏感。相反，miR-521的异位抑制导致前列腺癌细胞的辐射抗性。为了确定miR-521调节辐射敏感性的机制，我们测量了其预测靶点之一Cockayne综合征蛋白A（CSA）的表达水平。CSA是一种DNA修复蛋白，其水平与miR-521的水平呈负相关。放射治疗下调miR-521的水平，上调CSA蛋白。类似地，miR-521的异位抑制导致CSA蛋白水平增加。因此，通过改变CSA蛋白的水平，miR-521使前列腺癌细胞对放射治疗敏感。miR-521调节DNA修复蛋白CSA的表达水平，在前列腺癌细胞系的放射敏感性中起重要作用。因此，miR-521可能是增强放射治疗对前列腺癌细胞的作用的潜在靶点。
MicroRNAs (miRNA) are gene regulators and play an important role in response to cellular stress. Using multiplexed quantitative real-time PCR we performed global miRNA screening of prostate cancer cells in response to radiation treatment. Several miRNA were significantly altered in response to radiation treatment. Significant changes were observed in miR-521 and miR-34c. To determine the role of miR-521 in radiation response we transiently overexpressed miR-521 using miR-521 mimic. The miR-521 mimic significantly sensitized prostate cancer cells to radiation treatment. Conversely, ectopic inhibition of miR-521 resulted in radiation resistance of prostate cancer cells. To determine the mechanism by which miR-521 modulates radiation sensitivity we measured the expression levels of one of its predicted targets, Cockayne syndrome protein A (CSA). CSA is a DNA repair protein, and its levels correlated inversely with the levels of miR-521. Radiation treatment downregulated the levels of miR-521 and upregulated CSA protein. Similarly, ectopic inhibition of miR-521 resulted in increased CSA protein levels. Therefore by altering the levels of CSA protein, miR-521 sensitized prostate cancer cells to radiation treatment. miR-521 modulates the expression levels of DNA repair protein, CSA and plays an important role in the radiosensitivity of prostate cancer cell lines. Thus miR-521 can be a potential target for enhancing the effect of radiation treatment on prostate cancer cells.
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影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
DOI：
10.1098/rstb.1995.0012
发表时间：
1995-01-30
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BOOTSMA, D;WEEDA, G;HOEIJMAKERS, J
通讯作者：
HOEIJMAKERS, J
影响因子：
11.2
作者：
Huang, Wen-Chin;Wu, Daqing;Chung, Leland W. K.
通讯作者：
Chung, Leland W. K.
影响因子：
11.2
作者：
Marsit, Carmen J.;Eddy, Karen;Kelsey, Karl T.
通讯作者：
Kelsey, Karl T.
影响因子：
11.2
作者：
Weidhaas, Joanne B.;Babar, Lmran;Slack, Frank J.
通讯作者：
Slack, Frank J.