期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 217, 期 3, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20190950
关键词
-
资金
- National Scientific Foundation of China [81772544, 81972649]
- Science Foundation for Distinguished Young Scholars in Jiangsu [BK20160008]
- Priority Academic ProgramDevelopment of Jiangsu Higher Education Institutions
- National Key R&D Program of China [2016YFC1302100]
- Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2017ZT07S096]
Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) with the most aggressive phenotype and poor overall survival. Using bioinformatics tools, we identified LINC00908 encoding a 60-aa polypeptide and differentially expressed in TNBC tissues. We named this endogenously expressed polypeptide ASRPS (a small regulatory peptide of STAT3). ASRPS expression was down-regulated in TNBCs and associated with poor overall survival. We showed that LINC00908 was directly regulated by ERa, which was responsible for the differential down-regulation of LINC00908 in TNBCs. ASRPS directly bound to STAT3 through the coiled coil domain (CCD) and down-regulated STAT3 phosphorylation, which led to reduced expression of VEGF. In human endothelial cells, a mouse xenograft breast cancer model, and a mouse spontaneous BC model, ASRPS expression reduced angiogenesis. In a mouse xenograft breast cancer model, down-regulation of ASRPS promoted tumor growth, and ASRPS acted as an antitumor peptide. We presented strong evidence that LINC00908-encoded polypeptide ASRPS represented a TNBC-specific target for treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据