Proliferation-associated long noncoding RNA,TMPO-AS1, is a potential therapeutic target for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer compared with luminal or epidermal growth factor receptor 2 subtypes, thus effective therapeutic options for TNBC are yet to be developed. Nowadays, oncogenic long noncoding RNAs (lncRNAs) are applied to cancer management as a new class of therapeutic targets. We previously showed that thymopoietin antisense transcript 1 (TMPO-AS1) is a proliferation-associated lncRNA that contributes to hormone-dependent breast cancer progression by stabilizing estrogen receptor-alpha mRNA. We here showed thatTMPO-AS1is abundantly expressed in basal-like breast cancer subtype based on the transcriptomic data in The Cancer Genome Atlas as well as in TNBC cell lines and patient-derived cells. Small interfering RNA-based loss-of-function analyses showed thatTMPO-AS1knockdown substantially represses the proliferation and migration of TNBC cells. Expression microarray analysis showed thatTMPO-AS1alters gene signatures related to transforming growth factor-beta signaling in addition to proliferative E2F signaling pathways.TMPO-AS1-targeted siRNA treatment through engineered drug delivery systems using cancer-targeted polyion complex micelle or nanoball technology significantly impaired the in vivo growth of primary and metastatic TNBC xenograft tumors. Our findings suggest thatTMPO-AS1plays a key role in TNBC pathophysiology and could be a potential therapeutic target for TNBC.