Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer

doi:10.1038/ncomms14917

	Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer
	Xue, Mengzhu 1; Liu, Haiyue 1; Zhang, Liwen1,2,3,4 ; Chang, Hongyuan 1,3; Liu, Yuwei 1; Du, Shaowei 1,5; Yang, Yingqun1,3,4 ; Wang, Peng1,2,3,4
	2017-04-11
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	8
发表状态	已发表
DOI	10.1038/ncomms14917
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.
收录类别	SCI
语种	英语
资助项目	Science and Technology Commission of Shanghai Municipality Project[16ZR1449000]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000398827000001
出版者	NATURE PUBLISHING GROUP
WOS关键词	GENE REGULATORY NETWORKS ; ANDROGEN RECEPTOR ; SUPER-ENHANCERS ; INTEGRATIVE ANALYSIS ; BREAST-CANCER ; CELL IDENTITY ; EXPRESSION ; RESISTANCE ; LANDSCAPE ; GENOMICS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1415
专题	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
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
通讯作者单位	生命科学与技术学院
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).