LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer

Autor: Sheng-Jia Shi, Yun-Hui Li, Bo Yu, Yong Jin, Xiao-Zhong Bai, Li-Juan Wang
Rok vydání: 2015
Předmět:
Time Factors
Breast cancer
Trastuzumab
Cell Movement
Transforming Growth Factor beta
Medicine
skin and connective tissue diseases
biology
EMT
Long non-coding RNA
Up-Regulation
Gene Expression Regulation
Neoplastic
Phenotype
Oncology
trastuzumab resistance
Female
RNA Interference
RNA
Long Noncoding
medicine.drug
Signal Transduction
Research Paper
TGF-β
Epithelial-Mesenchymal Transition
Antineoplastic Agents
Breast Neoplasms
Transfection
Downregulation and upregulation
Cell Line
Tumor
microRNA
Humans
Neoplasm Invasiveness
Epithelial–mesenchymal transition
neoplasms
Homeodomain Proteins
business.industry
Zinc Finger E-box-Binding Homeobox 1
Transforming growth factor beta
lnc-ATB
medicine.disease
MicroRNAs
Drug Resistance
Neoplasm
Immunology
Cancer research
biology.protein
Trans-Activators
business
Transforming growth factor
Transcription Factors
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Sheng-Jia Shi 1, * , Li-Juan Wang 2, * , Bo Yu 1 , Yun-Hui Li 1 , Yong Jin 1 , Xiao-Zhong Bai 1 1 Department of Administration and Department of Aristogenesis, No. 202 Hospital of PLA, No. 5, Shenyang, 110003, Liaoning Province, P.R. China 2 Department of Oncology, the First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi Province, P.R. China * These authors have contributed equally to this work Correspondence to: Xiao-Zhong Bai, e-mail: baixz2015@163.com Keywords: lnc-ATB, trastuzumab resistance, EMT, TGF-β, breast cancer Received: February 05, 2015 Accepted: February 25, 2015 Published: March 23, 2015 ABSTRACT Trastuzumab resistance is leading cause of mortality in HER2-positive breast cancers, and the role of TGF-β-induced epithelial-mesenchymal transition (EMT) in trastuzumab resistance is well established, but the involvement of lncRNAs in trastuzumab resistance is still unknown. Here, we generated trastuzumab-resistant breast cancer cells with increased invasiveness compared with parental cells, and observed robust epithelial–mesenchymal transition (EMT) and consistently elevated TGF-β signaling in these cells. We identified long noncoding RNA activated by TGF-β (lnc-ATB) was the most remarkably upregulated lncRNA in TR SKBR-3 cells and the tissues of TR breast cancer patients. We found that lnc-ATB could promote trastuzumab resistance and invasion-metastasis cascade in breast cancer by competitively biding miR-200c, up-regulating ZEB1 and ZNF-217, and then inducing EMT. In addition, we also found that the high level of lnc-ATB was correlated with trastuzumab resistance of breast cancer patients. Thus, these findings suggest that lncRNA-ATB, a mediator of TGF-β signaling, could predispose breast cancer patients to EMT and trastuzumab resistance.
Databáze: OpenAIRE
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