Abstract |
Recent studies indicate that the long noncoding RNA ATB (lncATB) can induce the epithelial-mesenchymal transition (EMT) in cancer cells, but the specific cellular targets of lncATB require further investigation. In the present study, the upregulation of lncATB in breast cancer cells was validated in a TGF-β-induced EMT model. Gain- and loss-of-function studies demonstrated that lncATB enhanced cell migration, invasion and clonogenicity in vitro and in vivo. LncATB promoted the EMT by acting as a sponge for the miR-200 family and restoring Twist1 expression. Subsequently, the clinical significance of lncATB was investigated in a cohort of breast cancer patients (N = 131). Higher lncATB expression was correlated with increased nodal metastasis (P = 0.036) and advanced clinical stage (P = 0.011) as well as shorter disease-free survival (P = 0.043) and overall survival (P = 0.046). These findings define Twist1 as a major target of lncATB in the induction of the EMT and highlight lncATB as a biomarker in breast cancer patients.
|
Authors | Rong-Hui Li, Min Chen, Jing Liu, Chang-Chun Shao, Cui-Ping Guo, Xiao-Long Wei, Yao-Chen Li, Wen-He Huang, Guo-Jun Zhang |
Journal | Cell death & disease
(Cell Death Dis)
Vol. 9
Issue 12
Pg. 1171
(12 05 2018)
ISSN: 2041-4889 [Electronic] England |
PMID | 30518916
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- MIRN200 microRNA, human
- MicroRNAs
- Nuclear Proteins
- RNA, Long Noncoding
- RNA, Small Interfering
- TWIST1 protein, human
- Transforming Growth Factor beta
- Twist-Related Protein 1
- long non-coding RNA ATB, human
|
Topics |
- Adult
- Animals
- Breast Neoplasms
(diagnosis, genetics, metabolism, mortality)
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Cohort Studies
- Epithelial-Mesenchymal Transition
(drug effects, genetics)
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Lymphatic Metastasis
- MCF-7 Cells
- Mice
- Mice, Nude
- MicroRNAs
(antagonists & inhibitors, genetics, metabolism)
- Middle Aged
- Neoplasm Invasiveness
- Neoplasm Staging
- Nuclear Proteins
(genetics, metabolism)
- Prognosis
- RNA, Long Noncoding
(genetics, metabolism)
- RNA, Small Interfering
(genetics, metabolism)
- Signal Transduction
- Survival Analysis
- Transforming Growth Factor beta
(pharmacology)
- Tumor Burden
- Twist-Related Protein 1
(genetics, metabolism)
- Xenograft Model Antitumor Assays
|