Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition
文献类型：期刊论文
| 作者 | Wang, J.1; He, J.1,2; Su, F.1; Ding, N.1,2; Hu, W.1,2; Yao, B.1,2; Wang, W.3; Zhou, G.1 |
| 刊名 | CELL DEATH & DISEASE
 |
| 出版日期 | 2013-06-01 |
| 卷号 | 4 |
| 关键词 | Atr Pathway Mir-185 Apoptosis Proliferation |
| ISSN号 | 2041-4889 |
| DOI | 10.1038/cddis.2013.227 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| WOS关键词 | DNA-DAMAGE RESPONSE ; MICRORNA EXPRESSION PATTERNS ; CELL-CYCLE ARREST ; GENOME INTEGRITY ; DOWN-REGULATION ; HUMAN CANCERS ; LUNG ; REPLICATION ; PROFILES ; TARGETS |
| 资助项目 | National Natural Science Foundation of China[10979062] ; National Natural Science Foundation of China[31270895] ; National Natural Science Foundation of China[U1232125] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000321111700050 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.186/handle/113462/48429]  |
| 专题 | 中国科学院近代物理研究所 |
| 通讯作者 | Zhou, G. |
| 作者单位 | 1.Chinese Acad Sci, Dept Space Radiobiol, Inst Modern Phys, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Gansu, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Lanzhou Univ, Hosp 2, Inst Urol, Lanzhou 730000, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, J.,He, J.,Su, F.,et al. Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition[J]. CELL DEATH & DISEASE,2013,4. |
| APA | Wang, J..,He, J..,Su, F..,Ding, N..,Hu, W..,...&Zhou, G..(2013).Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition.CELL DEATH & DISEASE,4. |
| MLA | Wang, J.,et al."Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition".CELL DEATH & DISEASE 4(2013). |
入库方式： OAI收割
来源：近代物理研究所
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