期刊
CANCER SCIENCE
卷 111, 期 7, 页码 2440-2450出版社
WILEY
DOI: 10.1111/cas.14498
关键词
breast cancer; DDS; lncRNA; TMPO-AS1; TNBC
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science [16K15496]
- JSPS [18J00252, 17K18061, 17H04205]
- Takeda Science Foundation
- Japan Agency for Medical Research and Development
- Grants-in-Aid for Scientific Research [16K15496, 18J00252, 17H04205, 17K18061] Funding Source: KAKEN
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据