Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition.
Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition.
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miR-185 对 ATR 通路的抑制增强了辐射诱导的细胞凋亡和增殖抑制
DOI：
10.1038/cddis.2013.227
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发表时间：
2013-06-27
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
Cellular responses to DNA damage induced by intrinsic and extrinsic genotoxic stresses are highly regulated by complex signaling pathways, such as activation of the phosphoinositide-3-kinase-like protein kinase family and their downstream genes. Disruption of these signaling pathways leads to genome instability and cell death, and thus may provide potential novel strategies for cancer therapy. Here, we find that the expression of a human microRNA (miRNA), hsa-miR-185, is downregulated in response to ionizing radiation. Elevation of miR-185 sensitizes renal cell carcinoma cells to X-rays both in vitro and in vivo. Bioinformatic analysis shows that the ATM-and Rad3-related (ATR) kinase, a master conductor of cellular responses to DNA damage and DNA replication stresses, is a target of miR-185. This prediction was validated by luciferase reporter and mutation assays. We also demonstrated that miR-185 negatively regulates ATR expression at post-transcriptional level. miR-185 enhances radiation-induced apoptosis and inhibition of proliferation by repressing ATR pathway. In conclusion, our findings indicate a previously unreported regulatory mechanism for ATR expression mediated by miR-185 and shed light on the potential application of miRNAs both as direct cancer therapeutics and as tools to sensitize tumor cells to radiotherapy.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
13.8
作者：
Flynn, Rachel Litman;Zou, Lee
通讯作者：
Zou, Lee
影响因子：
2.6
作者：
Choong, Meng Ling;Yang, Henry He;McNiece, Ian
通讯作者：
McNiece, Ian
DOI：
10.1152/ajpheart.00233.2008
发表时间：
2008-12-01
影响因子：
4.8
作者：
Asada, Satoshi;Takahashi, Tomosaburo;Oh, Hidemasa
通讯作者：
Oh, Hidemasa
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.