title: Upregulation of long non-coding RNA urothelial carcinoma associated 1 by CCAAT/enhancer binding protein α contributes to bladder cancer cell growth and reduced apoptosis.
abstract: Long non-coding RNA urothelial carcinoma associated 1 (lncRNA-UCA1) is upregulated in bladder cancer and plays a pivotal role in bladder cancer progression and metastasis. Recent studies and our research found that lncRNA-UCA1 may be an important biomarker and therapeutic target for bladder cancer. However, the molecular mechanism involved in the upregulation of lncRNA-UCA1 in bladder cancer is largely unknown. In the present study, we showed that lncRNA-UCA1 expression in bladder cancer cells was upregulated by transcription factor CCAAT/enhancer binding protein α (C/EBPα), which was the only candidate transcription factor simultaneously predicted by a total of five bioinformatical software programs. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay indicated that C/EBPα bound to the lncRNA-UCA1 core promoter region in vitro and in vivo. The luciferase assays further showed that there was a point mutation (A231G) in the C/EBPα binding site of the lncRNA-UCA1 core promoter in various bladder cancer cell lines, which in turn significantly increased the transcriptional activity of lncRNA-UCA1. We also demonstrated that C/EBPα siRNA treatment contributed to the downregulation of lncRNA-UCA1 expression, whereas overexpression of C/EBPα enhanced lncRNA-UCA1 expression. Furthermore, lncRNA-UCA1 transcriptional repression by C/EBPα siRNA sharply reduced cell viability and induced cell apoptosis in vitro. Collectively, our results provide a novel therapeutic strategy for bladder cancer by effectively interrupting the binding of the lncRNA-UCA1 promoter and certain transcription factors, so as to reverse the upregulation of lncRNA-UCA1 and prevent bladder cancer progression.
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Xue
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wu
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Shuwan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Shouzhen
authors.initials: S
authors.lastname: Wu
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Zhengkun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000235:genetics; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D022763:CCAAT-Enhancer-Binding Protein-alpha; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C515159:UCA1 RNA, human