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

Abstract

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‐α mRNA. We here showed that TMPO‐AS1 is 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 that TMPO‐AS1 knockdown substantially represses the proliferation and migration of TNBC cells. Expression microarray analysis showed that TMPO‐AS1 alters gene signatures related to transforming growth factor‐β 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 that TMPO‐AS1 plays a key role in TNBC pathophysiology and could be a potential therapeutic target for TNBC.