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

被引：30

作者：

Mitobe, Yuichi ^{[1
]}

Ikeda, Kazuhiro ^{[1
]}

Sato, Wataru ^{[1
]}

Kodama, Yukinobu ^{[2
]}

Naito, Mitsuru ^{[3
]}

Gotoh, Noriko ^{[4
]}

Miyata, Kanjiro ^{[5
]}

Kataoka, Kazunori ^{[6
,7
]}

Sasaki, Hitoshi ^{[2
]}

Horie-Inoue, Kuniko ^{[1
]}

Inoue, Satoshi ^{[1
,8
]}

机构：

[1] Saitama Med Univ, Res Ctr Genom Med, Div Gene Regulat & Signal Transduct, Saitama, Japan

[2] Nagasaki Univ Hosp, Dept Hosp Pharm, Nagasaki, Japan

[3] Univ Tokyo, Ctr Dis Biol & Integrat Med, Grad Sch Med, Tokyo, Japan

[4] Kanazawa Univ, Canc Res Inst, Div Canc Cell Biol, Kanazawa, Ishikawa, Japan

[5] Univ Tokyo, Grad Sch Engn, Dept Mat Engn, Tokyo, Japan

[6] Univ Tokyo, Inst Future Initiat, Tokyo, Japan

[7] Kawasaki Inst Ind Promot, Innovat Ctr Nanomed, Kawasaki, Kanagawa, Japan

[8] Tokyo Metropolitan Inst Gerontol, Dept Syst Aging Sci & Med, Tokyo, Japan

来源：

CANCER SCIENCE | 2020年 / 111卷 / 07期

基金：

日本学术振兴会;

关键词：

breast cancer; DDS; lncRNA; TMPO-AS1; TNBC; POLY-L-LYSINE; OPEN PLATFORM; BETA; RNA; EXPRESSION; SIRNA; DELIVERY; CELLS; MICELLES; DISEASE;

D O I：

10.1111/cas.14498

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2440 / 2450

页数：11