Human endogenous retroviruses (HERVs) play pivotal roles in the development of breast cancer. However, the detailed mechanisms of noncoding HERVs remain elusive. Here, our genome-wide transcriptome analysis of HERVs revealed that a primate long noncoding RNA, which we dubbed TROJAN, was highly expressed in human triple-negative breast cancer (TNBC). TROJAN promoted TNBC proliferation and invasion and indicated poor patient outcomes. We further confirmed that TROJAN could bind to ZMYND8, a metastasis-repressing factor, and increase its degradation through the ubiquitin-proteasome pathway by repelling ZNF592. TROJAN also epigenetically up-regulated metastasis-related genes in multiple cell lines. Correlations between TROJAN and ZMYND8 were subsequently confirmed in clinical samples. Furthermore, our study verified that antisense oligonucleotide therapy targeting TROJAN substantially suppressed TNBC progression in vivo. In conclusion, the long noncoding RNA TROJAN promotes TNBC progression and serves as a potential therapeutic target.
[1]Fudan Univ, Shanghai Canc Ctr, Dept Breast Surg, 270 Dong An Rd, Shanghai 200032, Peoples R China;
[2]Fudan Univ, Shanghai Canc Ctr, Canc Inst, 270 Dong An Rd, Shanghai 200032, Peoples R China;
[3]Fudan Univ, Shanghai Med Coll, Dept Oncol, 270 Dong An Rd, Shanghai 200032, Peoples R China;
[4]Fudan Univ, Shanghai Canc Ctr, Precis Canc Med Ctr, 270 Dong An Rd, Shanghai 200032, Peoples R China;
[5]Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China;
[6]Fudan Univ, Minist Educ, Key Lab Metab & Mol Med, Shanghai 200032, Peoples R China;
[7]Fudan Univ, Sch Basic Med Sci, Dept Cellular & Genet Med, Key Lab Epigenet, Shanghai 200032, Peoples R China;
[8]Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China;
[9]Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China
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