Long non-coding RNA FGF13-AS1 inhibits glycolysis and sternness properties of breast cancer cells through FGF13-AS1/IGF2BPs/Myc feedback loop

被引:123
作者
Ma, Fei [1 ]
Liu, Xu [1 ]
Zhou, Shibo [3 ]
Li, Wenjie [1 ]
Liu, Chunxiao [1 ]
Chadwick, Michelle [4 ]
Qian, Cheng [1 ,2 ]
机构
[1] Harbin Med Univ, Canc Hosp, Dept Breast Swgery, Harbin, Heilongjiang, Peoples R China
[2] Heilongjiang Acad Med Sci, Translat Med Res & Cooperat Ctr Northern China, Harbin, Heilongjiang, Peoples R China
[3] Harbin Med Univ, Affiliated Hosp 4, Dept Pharm, Harbin, Heilongjiang, Peoples R China
[4] Rutgers State Univ, Canc Inst New Jersey, New Brunswick, NJ USA
基金
中国国家自然科学基金;
关键词
Lnc FGF13-AS1; Metabolism; Stemness; c-Myc; C-MYC ONCOGENE; PROLIFERATION; INTERPLAY; HYPOXIA; GENOME;
D O I
10.1016/j.canlet.2019.02.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
LncRNAs have been proven to play crucial roles in various processes of breast cancer. LncRNA FGF13-AS1 has been identified as one of the 25 downregulated lncRNAs in breast cancer through analyzing data from two cohorts and TCGA by another group of our lab. In this study, we report that FGF13-AS1 expression is decreased in breast cancer tissue compared with corresponding normal tissue, and the downregulation of FGF13-AS1 is associated with poor prognosis. Functional studies show that FGF13-AS1 inhibits breast cancer cells proliferation, migration, and invasion by impairing glycolysis and sternness properties. Mechanistically, FGF13-AS1 reduces the half-life of c-Myc (Myc) mRNA by binding RNA-binding proteins, insulin-like growth factor 2 mRNA binding proteins (IGF2BPs) and disrupting the interaction between IGF2BPs and Myc mRNA. Furthermore, Myc transcriptionally inhibits FGF13-AS1, forming a feedback loop in this signaling pathway. These results reveal for the first time that FGF13-AS1 functions as a tumor suppressor by inhibiting glycolysis and sternness properties of breast cancer cells, and the FGF13-AS1/IGF2BPs/Myc feedback loop could be a novel therapeutic target for breast cancer patients.
引用
收藏
页码:63 / 75
页数:13
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