Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer
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
2017-04-11
Source PublicationNATURE COMMUNICATIONS
ISSN2041-1723
Volume8
Status已发表
DOI10.1038/ncomms14917
AbstractAndrogen-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.
Indexed BySCI
Language英语
Funding ProjectScience and Technology Commission of Shanghai Municipality Project[16ZR1449000]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000398827000001
PublisherNATURE PUBLISHING GROUP
WOS KeywordGENE REGULATORY NETWORKS ; ANDROGEN RECEPTOR ; SUPER-ENHANCERS ; INTEGRATIVE ANALYSIS ; BREAST-CANCER ; CELL IDENTITY ; EXPRESSION ; RESISTANCE ; LANDSCAPE ; GENOMICS
Original Document TypeArticle
Citation statistics
Cited Times:12[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1415
Collection生命科学与技术学院
生命科学与技术学院_特聘教授组_王鹏组
生命科学与技术学院_硕士生
生命科学与技术学院_博士生
Corresponding AuthorWang, Peng
Affiliation1.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
Corresponding Author AffilicationSchool of Life Science and Technology
Recommended Citation
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).
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