LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis
- J Exp Med. 2020 Mar 2;217(3):jem.20190950. doi: 10.1084/jem.20190950.
- 1. Department of Genetics, Medical College of Soochow University, Suzhou, China.
- 2. Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
- 3. Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
- 4. The State Key Lab of Respiratory Disease, The First Affiliated Hospital, The School of Public Health, Guangzhou Medical University, Guangzhou, China.
- # Contributed equally.
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.