LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis

作者：Yirong Wang, Siqi Wu, Xun Zhu, Liyuan Zhang, Jieqiong Deng, Fang Li, Binbin Guo, Shenghua Zhang, Rui Wu, Zheng Zhang, Kexin Wang, Jiachun Lü, Yifeng Zhou · 发表于：The Journal of Experimental Medicine · 年份：2019 · DOI：10.1084/jem.20190950 · 被引用次数：227 · 研究领域：Cancer-related molecular mechanisms research、RNA modifications and cancer、Cytokine Signaling Pathways and Interactions

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 ERα, 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.