网站地图 加入收藏 中文 English
 
首页 中心概况 组织机构 研究队伍 科学研究 人才培养 交流合作 支撑服务 人才招聘 下载专区 联系我们
当前位置:首页 - 交流合作 - 专题学术讲座
专题学术讲座
6月29日清华大学学术报告 - 何厚胜
发布时间:2018-06-27关键字:

 

6月29日清华大学学术报告 - 何厚胜

 

时间:2018-06-29 10:00-11:00

主讲人:何厚胜

主题:Genetic variation, noncoding RNA and chromatin regulationon

地点:清华大学医学院B323室


Abstract:

The prostate cancer (PCa) risk-associated single nucleotide polymorphism (SNP) rs11672691 is positively associated with aggressive disease at diagnosis. Here, we replicated the finding in a cohort of 127 intermediate risk PCa patients, showing that the risk variant is associated with increased risk of relapse after therapy. rs11672691 is located in the promoter region of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). We find that the risk variant is associated with decreased levels of PCAT19-short, but increased levels of PCAT19-long. Mechanistically, risk variants of rs11672691 and its linkage disequilibrium SNP rs887391 decrease binding of NKX3.1 and YY1 to the promoter of PCAT19-short, converting this region to an enhancer that loops to the PCAT19-long promoter. PCAT19-long interacts with HNRNPAB to activate a subset of cell cycle genes that are associated with PCa progression, thereby promoting cell proliferation, migration, tumor growth and metastasis in vitro and in vivo. Taken together, these findings reveal a novel risk SNP mediated promoter-enhancer switching mechanism underlying both initiation and progression of aggressive PCa.

Published:

J. Hua et al., Risk SNPs mediated promoter-enhancer switching promotes prostate cancer development and progression through lncRNA PCAT19. Cell. Accepted.

W. Han et al., Reactivation of androgen receptor-regulated lipid biosynthesis drives the progression of castration-resistant prostate cancer. Oncogene 37, 710-721 (2018).

Y. Liang et al., LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression. Cancer research 77, 5479-5490 (2017).

Y. Liu et al., Transcriptional Landscape of the Breast Cancer Cell Cycle. PNAS. 2017.  

 

 




版权所有 生命科学联合中心