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Tytuł:
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Long non-coding RNA MANCR is a target of BET bromodomain protein BRD4 and plays a critical role in cellular migration and invasion abilities of prostate cancer.
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Autorzy:
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Nagasawa M; Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan; Department of Urology, Shiga University of Medical Science, Shiga, Japan.
Tomimatsu K; Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan.
Terada K; Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan.
Kondo K; Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan.
Miyazaki K; Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Miyazaki M; Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Motooka D; Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Okuzaki D; Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Yoshida T; Department of Urology, Shiga University of Medical Science, Shiga, Japan.
Kageyama S; Department of Urology, Shiga University of Medical Science, Shiga, Japan.
Kawamoto H; Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Kawauchi A; Department of Urology, Shiga University of Medical Science, Shiga, Japan.
Agata Y; Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan. Electronic address: .
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Źródło:
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Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 May 21; Vol. 526 (1), pp. 128-134. Date of Electronic Publication: 2020 Mar 18.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
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MeSH Terms:
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Cell Movement*/drug effects
Cell Movement*/genetics
Cell Cycle Proteins/*metabolism
Prostatic Neoplasms/*metabolism
Prostatic Neoplasms/*pathology
RNA, Untranslated/*metabolism
Transcription Factors/*metabolism
Azepines/pharmacology ; Cell Line, Tumor ; Down-Regulation/drug effects ; Down-Regulation/genetics ; Enhancer Elements, Genetic/genetics ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Neoplasm Invasiveness ; Prostatic Neoplasms/genetics ; RNA, Untranslated/genetics ; Triazoles/pharmacology
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Contributed Indexing:
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Keywords: BET protein inhibitor; Epithelial-mesenchymal transition; MANCR; Prostate cancer; Super-enhancer; lncRNA
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Substance Nomenclature:
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0 ((+)-JQ1 compound)
0 (Azepines)
0 (BRD4 protein, human)
0 (Cell Cycle Proteins)
0 (RNA, Untranslated)
0 (Transcription Factors)
0 (Triazoles)
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Entry Date(s):
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Date Created: 20200323 Date Completed: 20201124 Latest Revision: 20201124
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Update Code:
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20240105
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DOI:
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10.1016/j.bbrc.2020.03.043
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PMID:
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32199616
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Androgen receptor (AR)-negative castration-resistant prostate cancer (CRPC) is highly aggressive and is resistant to most of the current therapies. Bromodomain and extra terminal domain (BET) protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. A BET inhibitor, JQ1, has been found to suppress the malignant phenotypes of prostate cancer cells, however, the target genes of JQ1 remain largely unknown. Here we show that SE-associated genes specific for AR-negative CRPC PC3 cells include genes involved in migration and invasion, and that JQ1 impairs migration and invasion of PC3 cells. We identified a long non-coding RNA, MANCR, which was markedly down-regulated by JQ1, and found that BRD4 binds to the MANCR locus. MANCR knockdown led to a significant decrease in migration and invasion of PC3 cells. Furthermore, RNA sequencing analysis revealed that expression of the genes involved in migration and invasion was altered by MANCR knockdown. In summary, our data demonstrate that MANCR plays a critical role in migration and invasion of PC3 cells.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
