Human endogenous retroviruses (HERVs) play pivotal roles in the development of breast cancer. However, the detailed mechanisms of noncoding HERVs remain elusive. We used RNA-Seq to analyze the transcription level of each HERV loci across the genome in eight pairs of triple negative breast cancer (TNBC) and normal breast tissues. We identified one LTR70, which we dubbed TROJAN, was a TNBC related HERV. We also found that HERVs could not be researched as families because each members from the same family had different expression patterns in TNBC. TROJAN promoted proliferation and invasion in TNBC cells and indicated poor outcomes in patients. Here, we confirmed that TROJAN regulated the progression of TNBC through multiple mechanisms, with ZMYND8, a metastasis-repressing factor, being one of the targets of TROJAN. TROJAN could bind to ZMYND8, promoting its degradation through ubiquitin-proteosome system, and downregulated the transcription level of EGFR, thus stimulating the metastasis of TNBC. The association of TROJAN, ZMYND8, and EGFR was subsequently confirmed in clinical samples. Furthermore, our study verified that the therapeutic delivery of antisense oligonucleotides targeting TROJAN significantly suppressed metastasis of TNBC in vivo. In conclusion, TROJAN promotes the progression of breast cancer and serves as a potential therapeutic target in TNBC.

Citation Format: Jin X, Xu X-E, Jiang Y-Z, Shao Z-M. Human endogenous retrovirus TROJAN promotes triple negative breast cancer progression and represents a potential therapeutic target [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-06-06.