title: Long Non-Coding RNA (lncRNA) Urothelial Carcinoma-Associated 1 (UCA1) Enhances Tamoxifen Resistance in Breast Cancer Cells via Inhibiting mTOR Signaling Pathway.
abstract: BACKGROUND Long non-coding RNA (lncRNA) UCA1 is an oncogene in breast cancer. The purpose of this study was to investigate the role of UCA1 in tamoxifen resistance of estrogen receptor positive breast cancer cells. MATERIAL AND METHODS Tamoxifen sensitive MCF-7 cells were transfected for UCA1 overexpression, while tamoxifen resistant LCC2 and LCC9 cells were transfected with UCA siRNA for UCA1 knockdown. qRT-PCR was performed to analyze UCA1 expression. CCK-8 assay, immunofluorescence staining of cleaved caspase-9, and flow cytometric analysis of Annexin V/PI staining were used to assess tamoxifen sensitivity. Western blot analysis was performed to detect p-AKT and p-mTOR expression. RESULTS LncRNA UCA1 was significantly upregulated in tamoxifen resistant breast cancer cells compared to tamoxifen sensitive cells. LCC2 and LCC9 cells transfected with UCA1 siRNA had significantly higher ratio of apoptosis after tamoxifen treatment. UCA1 siRNA significantly decreased the protein levels of p-AKT and p-mTOR in LCC2 and LCC9 cells. Enforced UCA1 expression substantially reduced tamoxifen induced apoptosis in MCF-7 cells, while rapamycin treatment abrogated the protective effect of UCA1. CONCLUSIONS UCA1 upregulation was associated with tamoxifen resistance in breast cancer. Mechanistically, UCA1 confers tamoxifen resistance to breast cancer cells partly via activating the mTOR signaling pathway.
authors.affiliation: Department of Breast Surgery, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Clinical Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China (mainland).
authors.forename: Chihua
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Breast Surgery, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Clinical Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China (mainland).
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018931:Antineoplastic Agents, Hormonal; D062085:RNA, Long Noncoding; C515159:UCA1 RNA, human; D013629:Tamoxifen; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases