| CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. | |
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MedLine Citation:
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PMID: 20423907 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Long non-coding RNA (lncRNA), highly up-regulated in liver cancer (HULC) plays an important role in tumorigenesis. Depletion of HULC resulted in a significant deregulation of several genes involved in liver cancer. Although up-regulation of HULC expression in hepatocellular carcinoma has been reported, the molecular mechanisms remain unknown. In this study, we used in vivo and in vitro approaches to characterize cancer-dependent alterations in the chromatin organization and find a CREB binding site (encompassing from -67 to -53 nt) in the core promoter. Besides, we also provided evidence that PKA pathway may involved in up-regulation of HULC. Furthermore, we demonstrated HULC may act as an endogenous 'sponge', which down-regulates a series of microRNAs (miRNAs) activities, including miR-372. Inhibition of miR-372 leads to reducing translational repression of its target gene, PRKACB, which in turn induces phosphorylation of CREB. Over-expression of miR-372 decreases the association of CREB with the proximal promoter, followed by the dissociation of P300, resulting in a change of the histone 'code', such as in deacetylation and methylation. The study elucidates that fine tuning of HULC expression is part of an auto-regulatory loop in which it's inhibitory to expression and activity of miR-372 allows lncRNA up-regulated expression in liver cancer. |
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Authors:
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Jiayi Wang; Xiangfan Liu; Huacheng Wu; Peihua Ni; Zhidong Gu; Yongxia Qiao; Ning Chen; Fenyong Sun; Qishi Fan |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-27 |
Journal Detail:
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Title: Nucleic acids research Volume: 38 ISSN: 1362-4962 ISO Abbreviation: Nucleic Acids Res. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-13 Completed Date: 2010-10-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0411011 Medline TA: Nucleic Acids Res Country: England |
Other Details:
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Languages: eng Pagination: 5366-83 Citation Subset: IM |
Affiliation:
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Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Carcinoma, Hepatocellular / genetics*, metabolism Cell Line, Tumor Chromatin / chemistry Cyclic AMP Response Element-Binding Protein / metabolism* Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / genetics Cyclic AMP-Dependent Protein Kinases / metabolism Gene Expression Regulation, Neoplastic* Histones / metabolism Humans Liver Neoplasms / genetics*, metabolism MicroRNAs / metabolism* Promoter Regions, Genetic RNA, Untranslated / biosynthesis, genetics* Transcription Factors / metabolism Transcription Initiation Site Transcription, Genetic Transcriptional Activation Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Chromatin; 0/Cyclic AMP Response Element-Binding Protein; 0/Histones; 0/MicroRNAs; 0/RNA, Untranslated; 0/Transcription Factors; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.11/PRKACB protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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