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URL Address
<a href="http://doi.org/10.1194/jlr.M004531" target="_blank" rel="noreferrer noopener">http://doi.org/10.1194/jlr.M004531</a>
Pages
2223–2233
Issue
8
Volume
51
Dublin Core
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Title
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A putative role of micro RNA in regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes.
Publisher
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Journal of lipid research
Date
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2010
2010-08
Subject
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3' Untranslated Regions/genetics; Base Sequence; Chenodeoxycholic Acid/pharmacology; Cholesterol 7-alpha-Hydroxylase/*genetics; Enzymologic/drug effects/*genetics; Fibroblast Growth Factors/pharmacology; Gene Expression Regulation; Genetic/drug effects/genetics; Hep G2 Cells; Hepatocytes/drug effects/enzymology/*metabolism; Humans; Isoxazoles/pharmacology; MicroRNAs/*genetics/*metabolism; Oligonucleotide Array Sequence Analysis; Post-Transcriptional/drug effects/genetics; RNA Processing; Transcription
Creator
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Song Kwang-Hoon; Li Tiangang; Owsley Erika; Chiang John Y L
Description
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Cholesterol 7alpha-hydroxylase (CYP7A1) plays a critical role in regulation of bile acid synthesis in the liver. CYP7A1 mRNAs have very short half-lives, and bile acids destabilize CYP7A1 mRNA via the 3'-untranslated region (3'-UTR). However, the underlying mechanism of translational regulation of CYP7A1 mRNA remains unknown. Screening of a human micro RNA (miRNA) microarray has identified five differentially expressed miRNAs in human primary hepatocytes treated with chenodeoxycholic acid, GW4064, or fibroblast growth factor (FGF)19. These compounds also significantly induced the expression of miR-122a, a liver-specific and the predominant miRNA in human hepatocytes. The putative recognition sequences for miR-122a and miR-422a were localized in the 3'-UTR of human CYP7A1 mRNA. The miR-122a and miR-422a mimics inhibited, whereas their inhibitors stimulated CYP7A1 mRNA expression. These miRNAs specifically inhibited the activity of the CYP7A1-3'-UTR reporter plasmids, and mutations of miRNA binding sites in 3'-UTR abrogated miRNA inhibition of reporter activity. These results suggest that miR-122a and miR-422a may destabilize CYP7A1 mRNA to inhibit CYP7A1 expression. However, these miRNAs did not play a role in mediating FGF19 inhibition of CYP7A1 transcription. Under certain conditions, miRNA may reduce CYP7A1 mRNA stability to inhibit bile acid synthesis, and the miR-122a antagomirs may stimulate bile acid synthesis to reduce serum cholesterol and triglycerides.
Identifier
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<a href="http://doi.org/10.1194/jlr.M004531" target="_blank" rel="noreferrer noopener">10.1194/jlr.M004531</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2010
3' Untranslated Regions/genetics
Base Sequence
Chenodeoxycholic Acid/pharmacology
Chiang John Y L
Cholesterol 7-alpha-Hydroxylase/*genetics
Department of Integrative Medical Sciences
Enzymologic/drug effects/*genetics
Fibroblast Growth Factors/pharmacology
Gene Expression Regulation
Genetic/drug effects/genetics
Hep G2 Cells
Hepatocytes/drug effects/enzymology/*metabolism
Humans
Isoxazoles/pharmacology
Journal of lipid research
Li Tiangang
MicroRNAs/*genetics/*metabolism
NEOMED College of Medicine
Oligonucleotide Array Sequence Analysis
Owsley Erika
Post-Transcriptional/drug effects/genetics
RNA Processing
Song Kwang-Hoon
Transcription