Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer
文献类型：期刊论文
| 作者 | Xue, Mengzhu1; Liu, Haiyue1; Zhang, Liwen1,2,3,4; Chang, Hongyuan1,3; Liu, Yuwei1; Du, Shaowei1,5; Yang, Yingqun1,3,4; Wang, Peng1,2,3,4 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2017-04-11 |
| 卷号 | 8 |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/ncomms14917 |
| 文献子类 | Article |
| 英文摘要 | Androgen-ablation therapies, which are the standard treatment for metastatic prostate cancer, invariably lead to acquired resistance. Hence, a systematic identification of additional drivers may provide useful insights into the development of effective therapies. Numerous microRNAs that are critical for metastasis are dysregulated in metastatic prostate cancer, but the underlying molecular mechanism is poorly understood. We perform an integrative analysis of transcription factor (TF) and microRNA expression profiles and computationally identify three master TFs, AR, HOXC6 and NKX2-2, which induce the aberrant metastatic microRNA expression in a mutually exclusive fashion. Experimental validations confirm that the three TFs co-dysregulate a large number of metastasis-associated microRNAs. Moreover, their overexpression substantially enhances cell motility and is consistently associated with a poor clinical outcome. Finally, the mutually exclusive overexpression between AR, HOXC6 and NKX2-2 is preserved across various tissues and cancers, suggesting that mutual exclusivity may represent an intrinsic characteristic of driver TFs during tumorigenesis. |
| WOS关键词 | GENE REGULATORY NETWORKS ; ANDROGEN RECEPTOR ; SUPER-ENHANCERS ; INTEGRATIVE ANALYSIS ; BREAST-CANCER ; CELL IDENTITY ; EXPRESSION ; RESISTANCE ; LANDSCAPE ; GENOMICS |
| 资助项目 | National Natural Science Foundation of China (NSFC)[31271413] ; Science and Technology Commission of Shanghai Municipality Project[16ZR1449000] ; Chinese Academy of Sciences[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000398827000001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272704]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Peng |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Adv Res Inst, Lab Syst Biol, 100 Haike Rd,Zhangjiang Hi Tech Pk, Shanghai 201210, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd,Zhang Jiang Hi Tech Pk, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, Coll Life Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 4.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China; 5.Shanghai Univ, Sch Life Sci, 99 Shangda Rd, Shanghai 200444, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xue, Mengzhu,Liu, Haiyue,Zhang, Liwen,et al. Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer[J]. NATURE COMMUNICATIONS,2017,8. |
| APA | Xue, Mengzhu.,Liu, Haiyue.,Zhang, Liwen.,Chang, Hongyuan.,Liu, Yuwei.,...&Wang, Peng.(2017).Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer.NATURE COMMUNICATIONS,8. |
| MLA | Xue, Mengzhu,et al."Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer".NATURE COMMUNICATIONS 8(2017). |
入库方式： OAI收割
来源：上海药物研究所
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