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.
LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis
Y. Wang, S. Wu, X. Zhu, and L. Zhang contributed equally to this paper.
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Yirong Wang, Siqi Wu, Xun Zhu, Liyuan Zhang, Jieqiong Deng, Fang Li, Binbin Guo, Shenghua Zhang, Rui Wu, Zheng Zhang, Kexin Wang, Jiachun Lu, Yifeng Zhou; LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis. J Exp Med 2 March 2020; 217 (3): e20190950. doi: https://doi.org/10.1084/jem.20190950
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