title: LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer.
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.
authors: Department of Administration and Department of Aristogenesis, No. 202 Hospital of PLA, No. 5, Shenyang, 110003, Liaoning Province, P.R. China.
authors: Sheng-Jia
authors: SJ
authors: Shi
authors: Department of Oncology, the First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, P.R. China.
authors: Li-Juan
authors: LJ
authors: Wang
authors: Department of Administration and Department of Aristogenesis, No. 202 Hospital of PLA, No. 5, Shenyang, 110003, Liaoning Province, P.R. China.
authors: Bo
authors: B
authors: Yu
authors: Department of Administration and Department of Aristogenesis, No. 202 Hospital of PLA, No. 5, Shenyang, 110003, Liaoning Province, P.R. China.
authors: Yun-Hui
authors: YH
authors: Li
authors: Department of Administration and Department of Aristogenesis, No. 202 Hospital of PLA, No. 5, Shenyang, 110003, Liaoning Province, P.R. China.
authors: Yong
authors: Y
authors: Jin
authors: Department of Administration and Department of Aristogenesis, No. 202 Hospital of PLA, No. 5, Shenyang, 110003, Liaoning Province, P.R. China.
authors: Xiao-Zhong
authors: XZ
authors: Bai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010641:Phenotype; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000068878:Trastuzumab / Q000494:pharmacology*; D015854:Up-Regulation; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D000970:Antineoplastic Agents; D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C486307:ZEB1 protein, human; C113698:ZNF217 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000068878:Trastuzumab
keywords: EMT; TGF-β; breast cancer; lnc-ATB; trastuzumab resistance