title: Long non-coding RNA urothelial carcinoma associated 1 induces cell replication by inhibiting BRG1 in 5637 cells.
abstract: Long non-coding RNA urothelial carcinoma associated 1 (UCA1) was first identified in bladder cancer tissues. High expression of UCA1 in bladder cancer has suggested it may serve as a potential diagnostic molecular marker for bladder cancer. Subsequent research in bladder cancer cell lines showed that UCA1 can promote cell proliferation, but the underlying mechanism remains unknown. In the present study, we identified BRG1 as a UCA1 binding partner using an in vitro RNA pull-down assay, and RNA-binding protein immunoprecipitation assay confirmed UCA1-BRG binding in bladder cancer cells in vivo. BRG1 is a chromatin remodeling factor with reported tumor suppressor activities that directly upregulates levels of the p21 cell cycle inhibitor by binding sequences in the p21 promoter. Depletion of UCA1 by RNAi resulted in upregulated p21 levels and inhibition of cell replication, while overexpressed UCA1 reduced p21 protein and promoted cell growth. Notably, UCA1 downregulation of p21 and induction of cell proliferation antagonized the function of BRG1. UCA1 highly expressed tissue samples are often with BRG1 high expression. Furthermore, we found that UCA1 impairs both binding of BRG1 to the p21 promoter and chromatin remodeling activity of BRG1. Collectively, these results demonstrate that UCA1 promotes bladder cancer cell proliferation by inhibiting BRG1.
authors.affiliation: Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, Beijing 100191, P.R. China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, Beijing 100191, P.R. China.
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, Beijing 100191, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.affiliation: Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, Beijing 100191, P.R. China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, Beijing 100191, P.R. China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, Beijing 100191, P.R. China.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing 100034, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, Beijing 100191, P.R. China.
authors.forename: Zebin
authors.initials: Z
authors.lastname: Mao
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D014157:Transcription Factors; C515159:UCA1 RNA, human; C084108:SMARCA4 protein, human; D004265:DNA Helicases